Lumpectomy For Breast Cancer Research Articles

Rapid histopathological imaging of skin and breast cancer surgical specimens using immersion microscopy with ultraviolet surface excitation

Rapid histopathological evaluation of fresh, unfixed human tissue using optical sectioning microscopy would have applications to intraoperative surgical margin assessment. Microscopy with ultraviolet surface excitation (MUSE) is a low-cost optical sectioning technique using ultraviolet illumination which limits fluorescence excitation to the specimen surface. In this paper, we characterize MUSE using high incident angle, water immersion illumination to improve sectioning. Propidium iodide is used as a nuclear stain and eosin yellow as a counterstain. Histologic features of specimens using MUSE, nonlinear microscopy (NLM) and conventional hematoxylin and eosin (H&E) histology were evaluated by pathologists to assess potential application in Mohs surgery for skin cancer and lumpectomy for breast cancer. MUSE images of basal cell carcinoma showed high correspondence with frozen section H&E histology, suggesting that MUSE may be applicable to Mohs surgery. However, correspondence in breast tissue between MUSE and paraffin embedded H&E histology was limited due to the thicker optical sectioning in MUSE, suggesting that further development is needed for breast surgical applications. We further demonstrate that the transverse image resolution of MUSE is limited by the optical sectioning thickness and use co-registered NLM to quantify the improvement in MUSE optical sectioning from high incident angle water immersion illumination.

Abstract P2-11-14: IMRT use after lumpectomy in early-Stage breast cancer: Patterns of care and cost-consequences

Abstract BACKGROUND The American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation (CWr) against use of intensity modulated radiotherapy (IMRT) as part of breast conservation therapy in 2013, noting that “its routine use has not been demonstrated to provide significant clinical advantage”. Also, as IMRT is more expensive vs conventional radiotherapy (cRT), use in this setting may represent wasteful spending. The aims of this study were to characterize: 1) IMRT use immediately preceding the ASTRO CWr, 2) the cost-consequences of IMRT vs. cRT in the year after breast cancer diagnosis, and 3) excess annual U.S. national expenditure on IMRT in this setting. METHODS Surveillance Epidemiology and End Results (SEER) records for women age ≥66 years with a first primary diagnosis of Stage I/II breast cancer (2007-2012) were linked with Medicare claims (2007-2013). All cases had coverage for ≥12-months before/after diagnosis (or until death), and to be consistent with the CWr, had lumpectomy 1 month before to 6 months after diagnosis, and radiation therapy within 6 months of lumpectomy. We evaluated receipt of IMRT vs cRT within 1 year of diagnosis in 12 SEER registries. We also calculated mean direct medical expenditure in the year after diagnosis by summing all allowable charges from Medicare claims. Costs were inflated to 2017 USD. We evaluated differences in means by registry using ANOVA and compared mean costs for cases treated with IMRT vs cRT using t-test. We projected excess annual U.S. national expenditure on IMRT (vs. cRT) using the findings from aims 1 & 2 and assuming 209000 incident Stage I/II cases and that 55% receive lumpectomy. RESULTS Among 13037 women meeting all inclusion criteria, mean age was 74, 89.0% were white, and 19.8% received IMRT. Table 1 shows the proportions receiving IMRT by SEER registry and mean cost for cases treated with IMRT vs cRT. The proportion with IMRT varied significantly between registries (p<0.001), as did the mean cost for cases treated with IMRT (p<0.001) and cRT (p<0.001). Overall, cost for patients treated with IMRT was significantly higher vs those treated with cRT ($9644, p<0.001). Nationally, we estimated $219 million in annual excess medical expenditure on unnecessary IMRT vs. cRT. Table 1: Results for Selected RegistriesRegistry% with IMRTMean Cost in Year After Dx ($) IMRTcRTpAll 12 Registries19.84314533501<0.001California15.84624536039<0.001Detroit52.14138735704<0.001Georgia26.44047532257<0.001Iowa3.23884127567<0.001New Jersey25.24731135584<0.001Seattle5.84086332114<0.001 DISCUSSION From 2007-2013, use of IMRT in Stage I/II breast cancer was substantial (19.8%) and varied significantly across SEER registries. Cases treated with IMRT incurred significantly higher cost ($9644) in the year following diagnosis vs. those treated with cRT. If patterns of care remain similar today, there is potentially as much as $219 million in annual U.S. national expenditure on low-value radiotherapy following lumpectomy. Our findings suggest an opportunity to improve quality in cancer care while reducing expenditure by curbing use of IMRT. Future studies should develop interventions to align practice with ASTRO CW recommendations and reduce variation in practice between regions. Citation Format: Roth JA, McDougall J, Halasz L, Fedorenko C, Sun Q, Patel S. IMRT use after lumpectomy in early-Stage breast cancer: Patterns of care and cost-consequences [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-14.

Abstract P2-11-09: Excellent acute toxicity outcomes with proton therapy for partial breast irradiation in early stage breast cancer: Initial results of a multi-institutional phase II trial

Abstract Background and Purpose: Partial breast irradiation (PBI) with proton therapy after lumpectomy for early stage invasive breast cancer is an area of active investigation. Advantages of this technique include a shorter treatment course and the potential for decreased morbidity versus external beam photon radiation therapy given superior sparing of the surrounding normal breast tissue. To date, multiple single-institutional studies have reported conflicting results on the acute toxicity of PBI. This prospective phase II trial investigates the feasibility, safety, and efficacy of delivering PBI with proton therapy in a multi-institutional setting. Methods: Patients over the age of 50 years with ER-positive nonlobular invasive breast cancer or ductal carcinoma in situ ≤3 cm in size who had undergone lumpectomy with at least 2 mm negative surgical margins were treated with proton therapy to a dose of 40 Gy delivered over 10 daily fractions. In this initial analysis, we assess early toxicity and treatment efficacy of proton PBI. Patients were followed up at 4 weeks post-treatment and annually thereafter, along with annual mammograms. Patient-reported quality of life and physician-reported cosmesis assessments including photographs were obtained at 1 and 3 years post-treatment. Results: Forty patients were enrolled, of which 38 were evaluable. At a median follow-up of 17.8 months (range 2-36 months), all patients had overall breast cosmesis that was scored “good” or “excellent”. Of 6 grade 2 acute adverse events that occurred, only 1 was radiation dermatitis, with others including lymphedema, hot flashes, and fatigue. One grade 3 acute toxicity occurred 3 weeks after radiation completion in the form of vascular disease requiring stent placement, highly unlikely to be attributable to radiation effects. Patient-reported quality of life outcomes were recorded using the standardized Breast Cancer Treatment Outcome Scale (BCTOS) scored from 1-4 (1: none; 2: mild; 3: moderate; 4: large), with endpoints receiving a score of 3 or 4 most frequently involving change in breast size, breast texture, nipple appearance, or scar tissue. Patients assigned a score of 4 for change in nipple appearance (n=2), breast shape (n=2), and scar tissue formation (n=2). To date, local, locoregional, and distant disease control are 100%, although one patient has developed a new hormone receptor-negative invasive ductal carcinoma of the contralateral breast. Conclusion: Proton PBI provides excellent early cancer control with acceptable cosmetic outcomes and minimal adverse effects as per patient- and physician-reported assessments. On continued follow-up, late toxicity and cosmesis, as well as long-term disease control outcomes, will be assessed. Citation Format: Choi JI, Chang AL. Excellent acute toxicity outcomes with proton therapy for partial breast irradiation in early stage breast cancer: Initial results of a multi-institutional phase II trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-09.

Abstract P4-10-19: Disparities in use of adjuvant radiotherapy following lumpectomy among California regions

Abstract Background Women undergoing lumpectomy for invasive breast cancer typically receive radiotherapy (RT) to reduce risk of recurrence. Previous studies have reported disparities in the utilization of RT by race, socioeconomic status (SES), and age. In this study, we evaluate whether various sociodemographic factors are associated with use of RT in the different regions of California. Methods Utilizing data from the California Cancer Registry, the authors identified cases of women whose first primary invasive breast cancer was diagnosed between January 1, 2007 and December 31, 2012, whose primary surgery was breast conserving surgery, and for whom information was complete (n = 71,767). Multivariate logistic regression was used to determine whether demographic factors (SES, race, payer status, age) were significantly associated with use of RT following lumpectomy (p < .05), adjusting for tumor characteristics (size, stage, grade, hormone receptor status, and nodal status). Results In three out of eight regions in California, black race was associated with decreased odds of RT use (San Francisco, OR = 0.79, 95% CI = 0.68-0.92; Desert Sierra, OR = 0.72, 95% CI = 0.58-0.90; Los Angeles, OR = 0.78, 95% CI = 0.70-0.87). In Sacramento and Los Angeles regions, lower socioeconomic status was associated with declined odds of RT use. Age (70 years or older) was also associated with lower likelihood of RT use across all regions. Conclusions Even after accounting for payer status, racial and socioeconomic disparities persist in the use of RT. These disparities, previously documented in the time period of 2000-2007, have not disappeared. Hispanic race was not shown to be associated with decreased odds of RT use in Los Angeles, contrary to the results of a previous study. Women aged 70 years or older are less likely to receive RT. Citation Format: Huang RJ, Mukhtar RA, Alvarado M. Disparities in use of adjuvant radiotherapy following lumpectomy among California regions [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-19.

Abstract P2-12-05: Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity margins using the LUM imaging system: Results of a feasibility study

Abstract Background: Obtaining tumor-free margins is critical for local control in breast conserving surgery. Currently, 20-40% of lumpectomy patients have positive margins that require surgical re-excision. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor in breast cancer patients. The LUM System has the particular advantage of assessing in vivo lumpectomy cavity walls rather than excised specimens, to enable more accurate excision of residual tumor. Methods: Lumpectomy cavity walls of patients undergoing lumpectomy for invasive breast cancer or ductal carcinoma in situ (DCIS), were assessed intraoperatively using the LUM Imaging System (Lumicell Inc., Wellesley MA). LUM015, a cathepsin-activatable fluorescent agent, was given IV 4±2 hrs prior to surgery. Areas of fluorescence generated at potential sites of residual tumor in lumpectomy cavities were evaluated with a sterile hand-held device, displayed on a monitor, excised and correlated with histopathology. Results: In vivo lumpectomy cavities were imaged with the LUM Imaging System in 60 breast cancer patients. 5 were imaged without dye. 55 received LUM015 dye preoperatively and were scanned intraoperatively. Median age was 60 years (range 44-79). Mean tumor size was 1.2cm (0.06-3.5cm) with 71% invasive cancers, 29% DCIS. The test set included 569 cavity margin surfaces assessed intraoperatively and excised. Image acquisition for each margin took approximately 1 second. The LUM Imaging System showed 100% sensitivity and 73% specificity for detection of tumor <2mm from the margin. Invasive ductal cancer (IDC), invasive lobular cancer (ILC) and areas of DCIS 1mm in size could be identified. 8 patients had positive margins on standard histopathology analysis (Table). The LUM System correctly identified all positive margins identified by standard histopathology and correctly predicted negative re-excisions in 2 of 8 patients. There were no serious adverse events. 1 patient had extravasation of LUM015 at her injection site with temporary blue skin staining but no other complication. Conclusions: The LUM Imaging System allows real-time identification of residual tumor in the lumpectomy cavity of breast cancer patients. No sites of residual tumor were missed. Additional studies are underway to optimize this approach for reducing positive margins and second surgeries in breast cancer patients. Table: Margin results in 8 patients with positive margins on initial lumpectomy specimenPositive lumpectomy margin histopathologyLUM cavity wall result (+/- for tumor)Tumor found at re-excisionDCIS++DCIS+-DCIS++IDC++ (Mastectomy)ILC++ (Mastectomy)DCIS+-IDC--DCIS-- Citation Format: Lanahan CR, Gadd MA, Specht MC, Ferrer J, Tang R, Rai U, Merrill AL, Biernacka A, Brachtel E, Smith BL. Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity margins using the LUM imaging system: Results of a feasibility study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-05.

Factors Associated With Positive Margins in Women Undergoing Breast Conservation Surgery

ObjectiveTo identify factors predicting positive margins at lumpectomy prompting intraoperative reexcision in patients with breast cancer treated at a large referral center. Patients and MethodsWe reviewed all breast cancer lumpectomy cases managed at our institution from January 1, 2012, through December 31, 2013. Associations between rates of positive margin and patient and tumor factors were assessed using χ2 tests and univariate and adjusted multivariate logistic regression, stratified by ductal carcinoma in situ (DCIS) or invasive cancer. ResultsWe identified 382 patients who underwent lumpectomy for definitive surgical resection of breast cancer, 102 for DCIS and 280 for invasive cancer. Overall, 234 patients (61.3%) required intraoperative reexcision for positive margins. The reexcision rate was higher in patients with DCIS than in those with invasive disease (78.4% [80 of 102] vs 56.4% [158 of 280]; univariate odds ratio, 2.80; 95% CI, 1.66-4.76; P<.001). Positive margin rates did not vary by patient age, surgeon, estrogen receptor, progesterone receptor, or ERBB2 status of the tumor. Among the 280 cases of invasive breast cancer, the only factor independently associated with lower odds of margin positivity was seed localization vs no localization (P=.03). ConclusionDuctal carcinoma in situ was associated with a higher rate of positive margins at lumpectomy than invasive breast cancer on univariate analysis. Within invasive disease, seed localization was associated with lower rates of margin positivity.

Comparison of Propofol and Ketamine Combination (Ketofol) and Propofol and Fentanyl Combination (Fenofol) on Quality of Sedation and Analgesia in the Lumpectomy: A Randomized Clinical Trial.

Background:Breast lumpectomy is an integral part of the treatment of mammary masses in women. This study was conducted to evaluate and compare two-drug combinations of propofol–ketamine (PK) (ketofol) and propofol–fentanyl (PF) (fenofol) on quality of sedation and analgesia in lumpectomy.Materials and Methods:This was a randomized, double-blind, clinical trial performed on 64 patients aged 15–70 years with breast cancer lumpectomy referred to Isfahan's Seyed Al-Shohada Hospital. Consequently, patients were divided into two groups of 32 patients, each group receiving PF combination or PK combination during anesthesia.Results:The patients in two groups, PF and PK, were compared in their sedation levels, severity of pain, and other variables. The mean arterial blood pressure, systolic blood pressure, and heart rate (HR) did not show any significant difference at the beginning of the study in the two groups, but the fenofol (PF) group had a significantly lower oxygen saturation than the ketofol (PK) group. The sedation level was significantly lower in the fenofol group than the ketofol group (P < 0.001). The mean pain intensity was significantly lower in the PF group than the PK group (P < 0.001).Conclusion:The two combinations of ketofol and fenofol cause rapid, favorable, safe anesthetic with minimal side effects and hemodynamic effects but it may be a superior alternative to fenofol combination, in terms of respiratory depression.

Intraoperative radiation therapy as part of planned monotherapy for early-stage breast cancer

IntroductionAdjuvant whole breast radiation therapy has developed into the standard of care for patients following a lumpectomy for early-stage breast cancer. However, there is recent interest in intraoperative radiation therapy (IORT) to minimize toxicity while still improving local control beyond surgical resection and anti-estrogen therapy alone.Materials and methodsAll patients were evaluated pre-operatively in a multidisciplinary clinic setting at a community hospital for suitability for breast conservation therapy. A total of 109 patients were reviewed receiving 110 IORT treatments. Patients were followed with clinical breast examinations and mammography as clinically indicated.ResultsAt a median follow-up of 29.9 months, 2/110 (1.8%) patients experienced a local failure. One patient (0.9%) experienced a regional failure. Local control, disease-free survival and overall survival at 3 years were 98.9% (95%CI 92.2–99.8), 97.2% (95%CI 88.9–99.3), and 96.0% (95%CI 84.9–99.0), respectively. Five-year local control, disease-free survival, and overall survival rates were 96.3% (95%CI 84.7–99.2), 94.6% (95%CI 83.2–98.3), and 92.5% (95%CI 80.4–97.3), respectively. Patient self-reported cosmetic outcome was available for 51 patients, with all patients reporting being either very pleased, pleased, or satisfied with their cosmetic outcome, and no patients reported being dissatisfied or worse.ConclusionsThe results of our series suggest the feasibility of utilizing IORT in a community-based cancer center with a high degree of local control, and patient satisfaction with regard to cosmesis. While the results of this series suggest that IORT may be a promising modality, longer follow-up is warranted to better understand exactly which clinicopathological features can predict long-term locoregional disease control.

Automated detection of breast cancer in resected specimens with fluorescence lifetime imaging

Re-excision rates for breast cancer lumpectomy procedures are currently nearly 25% due to surgeons relying on inaccurate or incomplete methods of evaluating specimen margins. The objective of this study was to determine if cancer could be automatically detected in breast specimens from mastectomy and lumpectomy procedures by a classification algorithm that incorporated parameters derived from fluorescence lifetime imaging (FLIm). This study generated a database of co-registered histologic sections and FLIm data from breast cancer specimens (N = 20) and a support vector machine (SVM) classification algorithm able to automatically detect cancerous, fibrous, and adipose breast tissue. Classification accuracies were greater than 97% for automated detection of cancerous, fibrous, and adipose tissue from breast cancer specimens. The classification worked equally well for specimens scanned by hand or with a mechanical stage, demonstrating that the system could be used during surgery or on excised specimens. The ability of this technique to simply discriminate between cancerous and normal breast tissue, in particular to distinguish fibrous breast tissue from tumor, which is notoriously challenging for optical techniques, leads to the conclusion that FLIm has great potential to assess breast cancer margins. Identification of positive margins before waiting for complete histologic analysis could significantly reduce breast cancer re-excision rates.

The "Yin and Yang" of Platelet-rich Plasma in Breast Reconstruction After Mastectomy or Lumpectomy for Breast Cancer.

Surgery remains the mainstay of treatment for breast cancer, including complete or partial mastectomy and lumpectomy. Breast reconstruction has gained popularity mainly due to its tremendous impact on the psychological status of the patients. Autologous fat grafting is a well-established method used in cosmetic surgery; however, fat re-absoprtion, fat necrosis, calcifications and oil-cyst formation are some usually encountered complications limiting the efficacy of this approach. Platelet-rich plasma (PRP) has recently been postulated as a promising method for tissue regeneration since it contains high levels of diverse human growth factors. To date, preliminary results from clinical studies regarding the combination of PRP and fat grafting in breast reconstruction have shown ambiguous results, whereas preclinical studies are more favorable. However, concerns have been raised regarding the extent of cellular promotion induced by PRP application and the corresponding potential malignant transformation. The aim of our study was to present, analyze and critically evaluate the role of PRP in breast reconstruction after breast cancer surgery in terms of efficacy and oncological safety highlighting the caution that needs to be taken in order to eliminate any chance of recurrence in patients who have theoretically undergone complete excision of the tumor burden.

Abstract IA15: Molecular navigation for cancer diagnosis and surgery: Imaging tumors and nerves

Abstract Although treatment algorithms vary, surgery is the primary treatment modality for most solid cancers. The fundamental goal of a curative oncologic surgery is complete cancer removal but equally important from the patient's point of view is function preservation and pain control. Currently, there is an increasing trend to adopt minimally invasive technologies such as endoscopic and robotic surgery in order to decrease patient morbidity. However, the ability for surgeons to distinguish between normal and diseased tissue by texture or consistency is significantly reduced with these techniques (due to lack of ability to physically touch the tissue) and is limited to visual inspection alone. Using white light reflectance which is the current standard mode of illumination in operating rooms, the visual difference between normal and cancerous tissue can be imperceptible. The inability of surgeons to visually distinguish between tumor and normal tissue leads to residual cancer cells left behind at the edges of resection, i.e. positive surgical margins and can be as high as 20-40% in breast cancer lumpectomy, 21% for radical prostatectomy, and 13% for HNSCC. Molecular imaging with fluorescence provides enhanced visual definition between diseased and normal tissue and have been shown to decrease PSM in both animal models and patients. Molecular imaging with fluorescence can also provide enhanced visualization of important structures such as nerves to improve preservation and minimize inadvertent injury. Our laboratory has extensive experience in development of both nerve and tumor injectable markers for surgical visualization. In presentation we will discuss the development of nerve and tumor markers combinations to improve intraoperative visualization---aka color-coded surgery. Citation Format: Quyen T. Nguyen. Molecular navigation for cancer diagnosis and surgery: Imaging tumors and nerves [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA15.

Evaluating Radiation Omission Decisions in a Population-Based Sample of Older Adults Receiving Lumpectomy for Breast Cancer

Evaluating Radiation Omission Decisions in a Population-Based Sample of Older Adults Receiving Lumpectomy for Breast Cancer

Trends in Reoperation After Initial Lumpectomy for Breast Cancer

Surgery after initial lumpectomy to obtain more widely clear margins is common and may lead to mastectomy. To describe surgeons' approach to surgical margins for invasive breast cancer, and changes in postlumpectomy surgery rates, and final surgical treatment following a 2014 consensus statement endorsing a margin of "no ink on tumor." This was a population-based cohort survey study of 7303 eligible women ages 20 to 79 years with stage I and II breast cancer diagnosed in 2013 to 2015 and identified from the Georgia and Los Angeles County, California, Surveillance, Epidemiology, and End Results registries. A total of 5080 (70%) returned a survey. Those with bilateral disease, missing stage or treatment data, and with ductal carcinoma in situ were excluded, leaving 3729 patients in the analytic sample; 98% of these identified their attending surgeon. Between April 2015 and May 2016, 488 surgeons were surveyed regarding lumpectomy margins; 342 (70%) responded completely. Pathology reports of all patients having a second surgery and a 30% sample of those with 1 surgery were reviewed. Time trends were analyzed with multinomial regression models. Rates of final surgical procedure (lumpectomy, unilateral mastectomy, bilateral mastectomy) and rates of additional surgery after initial lumpectomy over time, and surgeon attitudes toward an adequate lumpectomy margin. The 67% rate of initial lumpectomy in the 3729 patient analytic sample was unchanged during the study. The rate of final lumpectomy increased by 13% from 2013 to 2015, accompanied by a decrease in unilateral and bilateral mastectomy (P = .002). Surgery after initial lumpectomy declined by 16% (P < .001). Pathology review documented no significant association between date of treatment and positive margins. Of 342 responding surgeons, 69% endorsed a margin of no ink on tumor to avoid reexcision in estrogen receptor-positive progesterone receptor-positive cancer and 63% for estrogen receptor-negative progesterone- receptor-negative cancer. Surgeons treating more than 50 breast cancers annually were significantly more likely to report this margin as adequate (85%; n = 105) compared with those treating 20 cases or fewer (55%; n = 131) (P < .001). Additional surgery after initial lumpectomy decreased markedly from 2013 to 2015 concomitant with dissemination of clinical guidelines endorsing a minimal negative margin. These findings suggest that surgeon-led initiatives to address potential overtreatment can reduce the burden of surgical management in patients with cancer.

Clinical case scenarios

A 45 year old woman asks advice about how her hot flushes can be dealt with. She is taking tamoxifen following lumpectomy and radiotherapy for breast cancer. What would be your initial recommendation?

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer.

Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States. Using the National Cancer Database, we identified women with T1-T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule. Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs. Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures.

Abstract P1-11-08: Tumor and procedural factors associated with positive margins at lumpectomy in women undergoing breast conservation surgery

Abstract Background: Negative margins are important in decreasing risk of local recurrence after breast conservation surgery. Further, positive margins on final pathology require a second operation, burdening patients and increasing costs. We identified factors predicting positive margins at lumpectomy prompting intraoperative re-excision in a large referral center. Methods With IRB approval we reviewed all breast cancer lumpectomy cases from January 2012 to December 2013. Associations between rates of positive margin (defined as tumor at ink) and patient and tumor factors were assessed using chi square tests and univariate and adjusted multivariable logistic regression, overall and stratified by DCIS or invasive cancer. Results 385 patients (105 DCIS and 280 invasive disease) were identified. Overall positive margin rate at lumpectomy requiring intraoperative re-excision was 62.3% and was higher in DCIS than in invasive disease (78.1% vs 56.4%, OR=2.78, p=0.001). Positive margin rates did not vary by surgeon, patient age, ER, PR or HER2 status of the tumor. On univariate analysis higher tumor grade was associated with a higher margin positive rate (grade 3 vs grade 1, OR=1.71, p=0.049). Within the 105 DCIS cases, no factors had statistically significantly different odds of positive margins on univariate or multivariable analysis. Within the 280 cases of invasive breast cancer, factors independently associated with lower odds of margin positivity were neoadjuvant chemotherapy (OR 0.30, p=0.037, relative to no neoadjuvant therapy) and seed localized excision (OR 0.24, p=0.03, relative to no localization). Multivariable Logistic Regression* Modeling DCISInvasive DiseaseVariableOdds RatioP-valueOdds RatioP-valueAge 50+ vs Age &amp;lt;502.860.111.590.23Grade 2 vs Grade 10.940.921.500.21Grade 3 vs Grade 13.250.121.580.37Estrogen Receptor Positive vs Negative3.950.221.640.42Progesterone Receptor Positive vs Negative0.840.871.110.84Her2 Positive vs Negative 1.270.68Stage T2 vs T1 2.540.45Stage T3 vs T1 2.180.69Ki67 &amp;lt;15% vs 15%+ 0.570.09Neoadjuvant Chemotherapy vs None 0.300.04Seed Localization vs No Localization 0.240.03Wire Localization vs No Localization 0.330.13Intraoperative Ultrasound vs No Localization 0.670.53*adjusted for individual surgeons (all p &amp;gt;0.05) Conclusion DCIS was associated with higher rate of positive margins at lumpectomy than invasive breast cancer. Within invasive disease, neoadjuvant chemotherapy and seed localization were associated with lower rates of margin positivity. Strategies to decrease positive margins would be best employed in cases of lumpectomy for DCIS and for invasive disease treated without neoadjuvant chemotherapy. Seed localization may be one strategy to lower positive margin rates. Citation Format: Boughey JC, Keeney MG, Glasgow AE, Keeney GL, Habermann EB. Tumor and procedural factors associated with positive margins at lumpectomy in women undergoing breast conservation surgery [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-08.

Oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy: a population-based study

Background: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison to lumpectomy and mastectomy.Material and methods: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded.Results: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively), the time from surgery to onset of adjuvant chemotherapy, nor total time from biopsy to the onset of adjuvant chemotherapy (mean time 52.7, 51.9 and 53.2 days, respectively).Conclusions: Our study shows that oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy in comparison with mastectomy and lumpectomy. Accordingly, patients should not be excluded from treatment with oncoplastic breast surgery due to concerns of delay in adjuvant chemotherapy.

Does neoadjuvant chemotherapy affect morbidity, mortality, reoperations, or readmissions in patients undergoing lumpectomy or mastectomy for breast cancer?

The influence of neoadjuvant chemotherapy (NAC) prior to breast cancer surgery on postoperative complications is unclear. Our objective was to determine whether NAC was associated with postoperative outcomes in patients undergoing lumpectomy or mastectomy without reconstruction. Patients meeting inclusion criteria were identified from the National Surgical Quality Improvement Program (NSQIP) database participant user files from 2005 through 2012, after which NSQIP discontinued the NAC variable. Primary outcome measures included a composite measure of morbidity and mortality (M&M) and reoperations and readmissions within 30 days of the index procedure. Rates of postoperative complications stratified by receipt of NAC were compared by χ2. A logistic regression model was then built that included confounding factors for M&M. There were 30,309 patients meeting inclusion criteria. NAC was not associated with any postoperative outcomes from 2005 through 2012, but it was associated with higher M&M in lumpectomy patients during 2011 to 2012 [P=0.011, odds ratio (OR) 2.579; 95% confidence interval (CI), 1.239-5.368]. The finding that NAC was associated with higher M&M in lumpectomy patients during 2011 to 2012 warrants further investigation. Therefore, we recommend that the NSQIP database reinstitute the NAC variable to allow monitoring during anticipated changes in chemotherapy agents and protocols.

Fewer Reoperations After Lumpectomy for Breast Cancer with Neoadjuvant Rather than Adjuvant Chemotherapy: A Report from the National Cancer Database

BackgroundReoperations occur frequently after initial lumpectomy for breast cancer. The authors hypothesized that the receipt of neoadjuvant chemotherapy (NAC) is associated with fewer reoperations.MethodsThe association between timing of chemotherapy and reoperation rates (ROR) after lumpectomy was investigated for patients with stages 1–3 breast cancer in the National Cancer Database (NCDB) from 2010 to 2013 by multivariable logistic regression modeling. Then propensity score-matching was performed.ResultsThe unadjusted ROR for 71,627 stages 1–3 patients was 11.4% for those who had NAC compared with 20.3% for those who had postoperative chemotherapy (p < 0.001) (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.49–0.57; p < 0.001). The ORs for the reoperations performed for patients with stages 1, 2, and 3 cancers who received NAC were respectively 0.65 (95% CI 0.56–0.75), 0.50 (95% CI 0.45–0.56), and 0.27 (95% CI 0.19–0.38) The p values for all were lower than 0.001.ConclusionFor a population of patients receiving chemotherapy, the receipt of chemotherapy before instead of after surgery was associated with fewer reoperations after initial lumpectomy for breast cancer.

Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing.

BackgroundThe rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent to the excised neoplasm is often used for this purpose as it is simultaneously collected and generally contains the same tissue type as the neoplasm. Following NGS analysis, we and others have frequently observed low-level somatic mutations in these non-neoplastic tissues, which may impose additional challenges to somatic mutation detection as it complicates germline variant filtering.MethodsWe hypothesized that the low-level somatic mutation observed in non-neoplastic tissues may be entirely or partially caused by inadvertent contamination by neoplastic cells during the surgical pathology gross assessment or tissue procurement process. To test this hypothesis, we applied a systematic protocol designed to collect multiple grossly non-neoplastic tissues using different methods surrounding each single neoplasm. The procedure was applied in two breast cancer lumpectomy specimens. In each case, all samples were first sequenced by whole-exome sequencing to identify somatic mutations in the neoplasm and determine their presence in the adjacent non-neoplastic tissues. We then generated ultra-deep coverage using targeted sequencing to assess the levels of contamination in non-neoplastic tissue samples collected under different conditions.ResultsContamination levels in non-neoplastic tissues ranged up to 3.5 and 20.9 % respectively in the two cases tested, with consistent pattern correlated with the manner of grossing and procurement. By carefully controlling the conditions of various steps during this process, we were able to eliminate any detectable contamination in both patients.ConclusionThe results demonstrated that the process of tissue procurement contributes to the level of contamination in non-neoplastic tissue, and contamination can be reduced to below detectable levels by using a carefully designed collection method. A standard protocol dedicated for acquiring adjacent non-neoplastic tissue that minimizes neoplasm contamination should be implemented for all somatic mutation detection studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-016-0226-1) contains supplementary material, which is available to authorized users.