Local Recurrence Of Breast Cancer Research Articles

Reoperations due to inadequate surgical margins and risk of local recurrence in breast cancer: comparison between conventional and oncoplastic breast conserving surgery

Background: This retrospective cohort study aims to evaluate insufficient surgical margins, re-operations and local recurrences after conventional or oncoplastic breast conserving surgery (BCS).

Yes-associated protein expression in paired primary and local recurrent breast cancer and its clinical significance

Yes-associated protein (YAP) protein acts as tumorigenic factor in many solid tumors, but the situation in breast cancer is under debate. Here, we would analyze its status in breast cancer. YAP expression in the 110 primary breast cancer and their paired local recurrent tumors was investigated. Clinicopathologic data for age, histologic grading, hormone status, lymph nodes and HER2 status were also gathered and analyzed. 46.4% (51/110) primary breast cancer tissues were positive for total YAP expression which was significantly higher than that in the recurrent tissues (10.9%; P < 0.05). The expression of total YAP protein in the primary breast cancer tissues was positively associated with the tumor size, especially in triple negative breast cancer (TNBC) subtype (P < 0.05). Higher total or nuclear YAP expression in the primary tumor was correlated with poor disease-free survival among patients with TNBC (P < 0.05). In the multivariate models, nuclear YAP expression was an independently prognostic factor in TNBC. High total or nuclear YAP expression predicts poor prognosis among patients with TNBC. It might be a therapeutic target for TNBC in the future.

Breast cancer surgery: when less is more

This brief review traces the evolution of breast cancer surgery from radical mastectomy (MTX) to breast conserving therapy (BCT) where wide local excision (WLE) of the cancer is combined with whole breast irradiation. The role of sentinel lymph node biopsy (SLNB) to assess the axilla as an alternative to more extensive axillary lymph node dissection (ALND) is examined. This review is a contemporary evaluation of these procedures (BCT, SLNB) and their impact on survival and in reduction of morbidity, and shows that local recurrence of breast cancer (BC) after BCT has been reduced to < 5% at 10-year follow-up when guidelines that excision margins should be free of microscopic cancer are followed and where patients receive whole breast irradiation together with systemic therapy after WLE. Over the past decade, studies of women with early BC entered on the SEER data base, the California Cancer Register and the Norwegian Cancer Registry have shown that overall survival (OS) and disease specific survival (DSS) are significantly better after BCT than following MTX. The improved survival after BCT compared to MTX cannot be attributed to radiation alone. The critical difference between these two procedures is the extent of dissection. Experimental studies using animal models have provided convincing evidences that the more extensive the tissue trauma, the greater the postoperative inflammatory cascade. This cascade of cytokines and growth factors impairs humoral immunity and enhances cancer cell survival and growth. The reduction in tissue trauma in patients undergoing BCT is a likely explanation for their improved survival. Compared to ALND, SLNB results in less lymphoedema, sensory loss and impaired shoulder function. For the clinically negative axilla, normal on palpation and imaging, SLNB is accurate in both the initial assessment and after neoadjuvant chemotherapy (NAC).

A Case of Intraoperative Navigation Using ICG Fluorescence Imaging Method to Identify Local Recurrence of Breast Cancer

A Case of Intraoperative Navigation Using ICG Fluorescence Imaging Method to Identify Local Recurrence of Breast Cancer

Using natural language processing and machine learning to identify breast cancer local recurrence

BackgroundIdentifying local recurrences in breast cancer from patient data sets is important for clinical research and practice. Developing a model using natural language processing and machine learning to identify local recurrences in breast cancer patients can reduce the time-consuming work of a manual chart review.MethodsWe design a novel concept-based filter and a prediction model to detect local recurrences using EHRs. In the training dataset, we manually review a development corpus of 50 progress notes and extract partial sentences that indicate breast cancer local recurrence. We process these partial sentences to obtain a set of Unified Medical Language System (UMLS) concepts using MetaMap, and we call it positive concept set. We apply MetaMap on patients’ progress notes and retain only the concepts that fall within the positive concept set. These features combined with the number of pathology reports recorded for each patient are used to train a support vector machine to identify local recurrences.ResultsWe compared our model with three baseline classifiers using either full MetaMap concepts, filtered MetaMap concepts, or bag of words. Our model achieved the best AUC (0.93 in cross-validation, 0.87 in held-out testing).ConclusionsCompared to a labor-intensive chart review, our model provides an automated way to identify breast cancer local recurrences. We expect that by minimally adapting the positive concept set, this study has the potential to be replicated at other institutions with a moderately sized training dataset.

Can Patients with Multiple Breast Cancers in the Same Breast Avoid Mastectomy by Having Multiple Lumpectomies to Achieve Equivalent Rates of Local Breast Cancer Recurrence? Response to the Preliminary Alliance 11102 Trial Report

Can Patients with Multiple Breast Cancers in the Same Breast Avoid Mastectomy by Having Multiple Lumpectomies to Achieve Equivalent Rates of Local Breast Cancer Recurrence? Response to the Preliminary Alliance 11102 Trial Report

Helical Tomotherapy (HT) for Postmastectomy Radiation Therapy (PMRT) Treatment after Implant Breast Reconstruction

To report our experience of using Helical Tomotherapy (HT) for postmastectomy radiation therapy (PMRT) treatment after immediate breast reconstruction (IBR) with implant. A total of 173 patients who underwent modified radical mastectomy for invasive breast cancer with or without IBR with retropectoral implants, received PMRT with HT at our institution between 2013 and 2015. PMRT with chest wall, supraclavicular and internal mammary lymph nodes irradiation was delivered to a dose of 50 Gy/25 fx. In the IBR group (n=87), the Planning Target Volume of chest wall (PTVcw) included subcutaneous tissue and pectoralis muscle plus margin, excluding the posterior side of the implant and the ribs, considering this volume as the main site of local recurrence of breast cancer. The treatment plans and outcomes were compared with those of 86 patients treated for PMRT by HT without IBR (control group). CW and Internal Mammary Nodes (IMN) coverage and doses to the organs at risk were compared between groups. Clinical outcomes were also assessed, including rate of reconstruction failure and prosthesis exchange. Coverage of chest wall was significantly improved in the IBR group in comparison with the group without reconstruction (V95% = 95.1 % versus 92.0 %; p<0.0001). There was no significant difference in the IMN coverage between the two groups (V95% = 93.1 % versus 92.4 %; p=0.3467). Irradiated volume of the ipsilateral lung was significantly decreased in the IBR group with a median V20Gy of 11.6 % compared with 15.2 % in the control group (p<0.0001). Similarly, the median V15Gy of the heart was significantly lower in the IBR group than in the control group (1.7 vs 2.5 %; p=0.0280). All neighboring organs received doses that remained well below tolerance levels. The treatment tolerance was acceptable without any definitive interruption and no grade 3 or 4 toxicity. The rate of reconstruction failure was 13,8% (n=12) and 33,3% of patient had implant replacement. After a median follow-up of 39.8 months, the locoregional recurrence rate was low in both groups (only 1 local and 3 regional relapses among the 87 patients in IBR group). Adequate and safe PMRT with Helical Tomotherapy can be offered to patients treated by mastectomy and IBR with retropectoral implants, with excellent dosimetric results and acceptable clinical outcomes.

ASO Author Reflections: Breast Cancer Local Recurrence Versus New Primary-Clinical Predictors and Prognostic Implications.

ASO Author Reflections: Breast Cancer Local Recurrence Versus New Primary-Clinical Predictors and Prognostic Implications.

ASO Author Reflections: Meta-Analysis of Local Recurrence of Invasive Breast Cancer After Electron Intraoperative Radiotherapy.

ASO Author Reflections: Meta-Analysis of Local Recurrence of Invasive Breast Cancer After Electron Intraoperative Radiotherapy.

Isolated ipsilateral local recurrence of breast cancer: predictive factors and prognostic impact.

Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points. Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes. Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA. When MVA was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years, in comparison with ≥ 5-years). ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.

RETRACTED ARTICLE: Identification of protein kinase inhibitors to reprogram breast cancer cells

Direct reversion of cancers into normal-like tissues is an ideal strategy for cancer treatment. Recent reports have showed that defined transcription factors can induce reprogramming of cancer cells into pluripotent stem cells, supporting this notion. Here, we have developed a reprogramming method that uses a conceptually unique strategy for breast cancer cell treatment. We have screened a kinase inhibitor library and found that Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR) kinase inhibitors can substitute for all transcription factors to be sufficient to reprogram breast cancer cells into progenitor cells. Furthermore, ROCK–mTOR inhibitors could reprogram breast cancer cells to another terminal lineage-adipogenic cells. Genome-wide transcriptional analysis shows that the induced fat-like cells have a profile different from breast cancer cells and similar to that of normal adipocytes. In vitro and in vivo tumorigenesis assays have shown that induced fat-like cells lose proliferation and tumorigenicity. Moreover, reprogramming treatment with ROCK–mTOR inhibitors prevents breast cancer local recurrence in mice. Currently, ROCK–mTOR inhibitors are already used as antitumor drugs in patients, thus, this reprogramming strategy has significant potential to move rapidly toward clinical trials for breast cancer treatment.

A national multicenter study on 1072 DCIS patients treated with breast-conserving surgery and whole breast radiotherapy (COBCG-01 study)

Background and purposeBreast-conserving surgery (BCS) and whole breast radiation (RT) with or without endocrine therapy (ET) represent the standard of care for ductal carcinoma in situ (DCIS). The use of adjuvant treatments after surgery is still controversial in this setting. We performed a retrospective multicenter analysis on a series of DCIS patients treated with BCS and adjuvant RT. Materials and methodsWe collected clinical data from nine Italian centers on 1072 women having a diagnosis of DCIS and treated between 1997 and 2012. We reported on the 5- and 10-year local recurrence (LR) rates, overall survival, and breast cancer specific survival (BCSS) employing the Kaplan–Meier method. ResultsAt a median follow-up of 8.4 years, 67 LR (6.3%) and 47 deaths (4.4%) were observed. LR rates at 5 and 10 years were 3.4% and 7.6%, respectively. BCSS rates at 5 and 10 years were 99.7% and 99.1%, respectively. At univariate regression analysis, postmenopausal state (p = 0.009), estrogen receptor (ER) (p = 0.0001) and progesterone receptor (p = 0.018) positivity and ET (p = 0.006) were inversely correlated with LR. Final surgical margins (FSM) status <1 mm was significantly correlated with higher LR (p = 0.003). At multivariate regression analysis postmenopausal state (p = 0.03), and ER positive (p = 0.045) maintained the significant favorable feature, while FSM <1 mm (p = 0.024) confirmed its negative impact on LR. ConclusionsOur real-life study pointed out the significant favorable prognostic role of postmenopausal state and ER positive status on LR occurrence. FSM <1 mm was significantly correlated to a higher chance to experience LR.

Abstract 657: ESR1 mutations abundance in local recurrence of endocrine-treated breast cancer

Abstract Emerging mutations in the ESR1 gene that encodes for estrogen receptor (ER) have been recently associated with resistance to endocrine therapy in ER positive metastatic breast cancer patients. These mutations promote the active conformation of the receptor, conferring resistance to endocrine therapy, and were associated with shorter progression free survival. ESR1 mutations were found to rarely exist in primary tumors (~1%) but are relatively common in metastatic, endocrine therapy-resistant lesions, with an estimated prevalence of ~10-50%. Nevertheless, not much is known about the incidence of these mutations in local recurrence (breast and adjacent lymph nodes) and its clinical significance. The objective of this study is to determine the prevalence of ESR1 mutations in local recurrence of endocrine-treated breast cancer patients. To this end, we collected a cohort of breast cancer patients that had at least one local or loco-regional recurrence during or after adjuvant endocrine treatment for primary breast cancer. We analyzed the 5 most common ESR1 hotspot mutations (D538G, L536R, Y537S/N/C) using droplet digital PCR technology in 44 samples from 34 patients (some of the patients had more than one recurrence). ESR1 mutations were identified in 10/34 (29%) patients. Specifically, mutations were distributed between D538G (5/34), Y537S+ D538G (4/34) and L536R (1/34). ESR1 Mutations developed after or on Tamoxifen only treatment in 50% of the positive patients (5/10 patients) and after or on Tamoxifen + Aromatase Inhibitor (AI) treatment in the other 50% (5/10 patients). Notably, one patient developed ESR1 mutation while on neoadjuvant endocrine therapy. ESR1 mutations persisted in local recurrence samples of mutation positive patients that had more than one local recurrence and the chance of detecting a mutation in patients that had more than one recurrence was higher than in those with a single recurrence. This study demonstrates that ESR1 mutations are common in local recurrence of hormone receptor positive breast cancer. Further studies to establish the clinical significance of these mutations and their impact on survival are underway. Since local recurrences are amenable to curative therapy, the identified unexpected high prevalence of ESR1 mutations at this stage of the disease may have important consequences for choosing the optimal adjuvant treatment option for these patients. Citation Format: Adi Zundelevich, Maya Dadiani, Smadar Kahana-Edwin, Moran Gadot, Tal Sela, Irina Marin, Daniela Necula, Anya Pavlovsky, Iris Barshack, Bella Kaufman, Einav N. Gal-Yam. ESR1 mutations abundance in local recurrence of endocrine-treated breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 657.

Local recurrence of breast cancer: conventionally fractionated partial external beam re-irradiation with curative intention.

To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of asecond breast-conserving therapy or following mastectomy. Between 03/2004 and 10/2016, 83breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. The median follow-up was 35months (range 3-143months). The median time interval between the first irradiation and re-RT was 117months (range 16-357months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T‑category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (<grade3). Re-RT with 45 Gy (1.8 Gy per fraction) for partial breast or mastectomy scar after the second surgery resulted in high local control rates and tolerable skin toxicity.

A phase IIB pre-surgical trial of oral tamoxifen (TAM) versus transdermal 4-hydroxytamoxifen (4-OHT) in women with DCIS of the breast.

TPS1595Background: Ductal carcinoma in situ (DCIS) is diagnosed in 60,000 women annually in the US. TAM is proven to reduce risk of local recurrence and new primary breast cancer in women with estr...

Local and Regional Breast Cancer Recurrences: Salvage Therapy Options in the New Era of Molecular Subtypes.

Isolated local or regional recurrence of breast cancer (BC) leads to an increased risk of metastases and decreased survival. Ipsilateral breast recurrence can occur at the initial tumor bed or in another quadrant of the breast. Depending on tumor patterns and molecular subtypes, the risk and time to onset of metastatic recurrence differs. HER2-positive and triple-negative (TNG) BC have a risk of locoregional relapse between six and eight times than luminal A. Thus, the management of local and locoregional relapses must take into account the prognostic factors for metastatic disease development. It is important to personalize the overall management, including or not systemic treatment according to the metastatic risk. All isolated recurrence cases should be treated with curative intent. Complete surgical resection is recommended whenever possible. Patients who did not receive postoperative irradiation during their initial management should receive full-dose radiotherapy to the chest wall and to the regional lymph nodes if appropriate. Overall, total mastectomy is the “gold standard” among patients who were previously treated by conservative surgery followed by radiation therapy. In terms of systemic therapy, the benefits of additional treatments are not conclusively proven in cases of isolated recurrence. The beneficial role of chemotherapy has been reported in at least one randomized trial, while endocrine therapy and anti-HER2 are common practice. This review will discuss salvage treatment options of local and locoregional recurrences in the new era of BC molecular subtypes.

Location of Recurrence in Women Treated with Conventionally Planned Whole Breast Radiotherapy

Whole breast radiotherapy (RT) following breast-conserving therapy is known to reduce local recurrence in early-stage breast cancer. Conventionally, the external palpable breast has been used as the clinical target volume (CTV). In the era of CT simulation/planning, post-operative tumour bed (cavity) localization is also important as it is a high risk area of local recurrence. This study evaluates the location of the tumour bed cavity and its relationship to the area of recurrence in women previously treated with whole breast RT without explicit delineation of the cavity. A consecutive sample of 50 women with breast tumours (Tis-T3,Nx-1) previously treated with whole breast RT+/-boost was identified. The planning CTV was based on patient's palpable breast wired with radio-opaque markers during CT simulation and treated to a minimum of 92% prescription dose (50Gy-25fx or 40/42.4Gy-16fx) using forward planned intensity modulated RT (IMRT). The tumour bed was retrospectively contoured and expanded by 10mm (excluding skin and lung) for the planning target volume (cPTV). Geographic miss was defined as any part of the target volume receiving <50% of the prescription dose (D50). Five-year follow-up and the location for local and/or distant recurrence were collected. Descriptive statistics and unpaired Student's t-tests were performed, p-values <0.05 were considered as statistically significant. Five (10%) women had geographic miss to the cavity contours (CAVmiss). Women with CAVmiss had cavities located in extreme aspects of the breast: lateral (3); medial (1); or superior (1). The median follow-up was 4.5years and time to failure was 3.5years (1 to 5 years). Within the CAVin cohort (45), 2 (6%) patients recurred locally within the ipsilateral breast (1-year and 3-year follow-up, respectively); 1 (3%) patient developed regional disease to the infraclavicular lymph nodes at 4-year follow-up, and 1 (3%) developed contralateral inflammatory breast disease at 4-year follow-up; 11 patients were lost to follow-up. Of the 5 women with CAVmiss: 1 developed local recurrence at the edge of the original fields near the tumour bed and regional disease to the axilla and supraclavicular nodal basins (4yr follow-up); 1 developed distance disease (3yr follow-up). Local recurrence can occur near the tumour bed following whole breast RT. Without delineation of the post-operative cavity, 10% of women had inadequate coverage to their tumor bed despite the use of standard tangential RT fields. The adoption of cavity delineation would reduce the risk of geographic miss and ensure the accuracy of radiotherapy.

Abstract P2-12-07: Local recurrence of breast cancer: Salvage lumpectomy as a safe option for local treatment

Abstract Introduction: The best local management for breast cancer recurrence following conservative treatment for breast cancer (BC) continues to be an open question. In this study, we compared patients' outcome after salvage lumpectomy vs. patients who underwent mastectomy for ipsilateral breast tumor recurrence (IBTR). Materials and methods: Between 1987 and 2014 we identified 121 patients with pT0-2, N0-3, M0 BC who had breast conserving surgery and radiation as their primary treatment, and subsequently had IBTR (unifocal). 47 patients underwent salvage lumpectomy (SL) and 74 salvage mastectomy (SM) as the local treatment for their 1st recurrence. Results: Median follow-up was 14 years (2-30) from first BC diagnosis. All consecutive identified patients, 121, were included in the study. At 1st recurrence, 47 patients (39%) chose to undergo SL for their IBTR, and 74 patients (61%) opted for SM. The mean age at 1st diagnosis of BC for SL group and SM, was 52 and 47 years, respectively (p=0.006). With similar T in both groups, most patients had T1 (43%), and T2 (34%) at first diagnosis (p=0.722). The women who opted later for SM had more ALND surgery (58% vs. 33%, p=0.023) and received more neoadjuvant chemotherapy (20% vs. 4%, p=0.022) at their first BC diagnosis. The median DFI at 1st recurrence for SL and SM group was 12 and 7 years, respectively (p=0.011). 51 local recurrences (41%) were true recurrences by location and histology. In the SL group, 78% had a documented discussion (consideration for SL vs. SM) with a surgeon/oncologist/radiation oncologist prior to surgical decision, and 70% underwent a breast MRI before final decision. Only 45% in the SM group had a discussion and 59% underwent MRI before the decision. Following surgery for their recurrence, sixteen women (34%) of SL group underwent re-irradiation (partial breast RT) and 20 (27%, p=0.04) in the SM group (chest wall scar). For the SL and SM cohorts, 8 and 10 patients (17%, 13.5%, p=0.22) respectively, developed subsequent local recurrence as a 3rd event. The median DFI between 2nd and 3rd recurrence for SL and SM was 6.5 and 15.5 years, respectively (p=0.081). In a multivariate analysis, age at 1st diagnosis, T at 1st and 2nd recurrence, number of dissected/+ve LN, grade, type of axillary surgery as well as neo/adjuvant chemotherapy and HER2 status (both in primary and at recurrence), had no effect on 2nd recurrence occurrence for both groups; however, in MVA, undergoing SL had higher chances of having a 2nd recurrence (3rd event), p=0.020. Having re-irradiation following SL did not protect against 2nd recurrence (3rd event, p=0.42). At a median follow-up of 14 years, 95.7% of SL patients are alive, NED, 85% are mastectomy free. 84% of patients who opted for SM are alive, NED. Conclusions: Salvage lumpectomy following IBTR, while associated in MVA with higher second local recurrence rate than SL is not associated with inferior survival. With survival &amp;gt;95% at 14 years in the SL cohort, salvage lumpectomy with or without re-radiation, in a selected population (unifocal T), represents an acceptable treatment option for patients in order to delay time to mastectomy and keep the original breast without reducing BC survival. Both options should be discussed prior to any surgical decision. Citation Format: Sellam Y, Akiva Ben David M, Galper S, Dromi Shahadi I, Zippel D, Symon Z, Gelernter I. Local recurrence of breast cancer: Salvage lumpectomy as a safe option for local treatment [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 P2-12-07.

Abstract P2-11-13: Meta-analysis of local recurrence of invasive breast cancer after electron intraoperative radiotherapy

Abstract Background: Electron intraoperative radiotherapy (IORT) can be used during breast conservation surgery to treat early-stage invasive breast cancer. While IORT may be an attractive alternative to traditional post-operative radiotherapy for many patients, its effectiveness in preventing local recurrence is still being evaluated. Using data from current clinical and observational studies, we aimed to assess the impact of single-fraction electron IORT on local recurrence rates. Methods: Studies on single-fraction electron IORT during breast conservation surgery were identified through a search of PubMed and Google Scholar, as well as secondary referencing. Local recurrence rate was the main outcome of interest. Protocols from each publication were assessed for potential sources of heterogeneity. A meta-analysis of proportions, using binomial distribution to model the within-study variability and a random effects model, was conducted to estimate a pooled local recurrence rate. In order to estimate a 5-year recurrence rate, we applied a single-sample Poisson-normal model to model the probability of events occurring during a fixed period of time (60 months). Results: A total of 13 independent publications were identified for abstraction. The analysis demonstrated a pooled monthly local recurrence rate of 0.02% per person-month (95% CI: 0.00 – 0.06%) for the studies with &amp;lt; 5 years of follow-up, 0.03% per person-month (0.02 – 0.06%) for studies with ≥ 5 years of follow-up, and 0.02% per person-month (0.01 – 0.04%) overall. Based on this model, the predicted 5-year recurrence rate is 2.7%, with a 95% confidence interval of 1.9% - 3.7%. Conclusions: According to the published literature, the rate of breast cancer local recurrence after electron IORT was 0.02% per person-month; with an adjusted 5-year recurrence rate of 2.7%. These findings support the recent guidelines from the American Society for Radiation Oncology (ASTRO) supporting the use of electron IORT in low-risk patients. Citation Format: Harness J, Shah C, Brooks E, Via C, Vicini F. Meta-analysis of local recurrence of invasive breast cancer after electron intraoperative radiotherapy [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 P2-11-13.

Abstract P5-02-02: Second harmonic generation in combination with nuclear morphometry in the evaluation of DCIS

Abstract Purpose/Objective: Collagen is a major extracellular matrix (ECM) constituent in normal breast and is extensively remodeled in breast carcinoma. Therefore, features of remodeled collagen in the stroma adjacent to ductal carcinoma in situ (DCIS) could indicate cancer progression. The major objective of this study is to identify potential tumor-associated collagen signatures unique to DCIS that will allow us to predict progression based on the collagen texture and nuclear morphology. In this present study, we develop two image analysis pipelines (SHG Texture Extraction and H&amp;E Nuclear Morphology Extractor) to quantify 1) stromal changes, 2) collagen signatures and 3) nuclear morphology from normal breast to DCIS in order to predict local breast cancer recurrence. Method: We used second harmonic generation (SHG) images and H&amp;E to analyze collagen features and to study nuclear morphology using a data set of 336 patients (from which 310 normal and 327 DCIS regions were imaged). The 336 patients were a subset of patients with pure DCIS taken from a case-control study. Clinical-pathologic factors were associated with risk of subsequent ipsilateral cancer (DCIS or invasive). The SHG framework consisted of collagen segmentation using 1) adaptive thresholding and 2) morphological operations. The H&amp;E framework consisted of nuclear segmentation using adaptive thresholding and a maker-controlled watershed algorithm; and nuclear feature extractions including intensity, texture and morphology. Overall, the SHG framework segments collagen regions and computes textural features specifically at collagen regions. Furthermore, the H&amp;E framework segments nuclei and computes nuclei morphology and textural features. These features were used in L1-regularized logistic regression to construct classification models to discriminate normal vs DCIS regions; and to distinguish regions from DCIS patients with vs. without local recurrences. Results: In first experiment, we performed L1-regularized logistic regression to construct a classification model to discriminate normal vs DCIS regions. Our results suggest that using only SHG collagen features, this logistic model selected 19 significant features to build a classification model that achieved area under curve (AUC) 90% and accuracy 83% using 5-Fold cross validation. When H&amp;E nuclei features are used, the logistic model selected 88 significant features and achieved AUC 91% and accuracy 86%. By combined both SHG and H&amp;E features, the model achieved classification AUC 93% and accuracy 88%. By using L1-regularized logistic model with combined significant SHG and H&amp;E features, we achieved AUC 59% with an accuracy of 61% for DCIS and recurrent DCIS regions. Conclusions: Our study suggests that SHG and nuclear morphology features extracted from H&amp;E can improve the classification of normal and DCIS regions. Overall, these results suggest that second harmonic generation and H&amp;E nuclear morphology analysis could aid in the assessment of prognosis and risk of progression to invasive breast cancer. Citation Format: Park CC, Irshad H, Ziaee S, Martin-Tuite P, Habel L, Weaver VM, Schnitt SJ, Beck AH. Second harmonic generation in combination with nuclear morphometry in the evaluation of DCIS [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 P5-02-02.