Localized Breast Research Articles

Persistent taxane-induced neuropathy in elderly patients treated for localized breast cancer.

Breast cancer is the most common cancer among women. Localized breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. A monocenter historical cohort study including all women over 65years of age treated between 2001 and 2016 with a taxane-based chemotherapy for localized breast cancer was carried out at the Paul Strauss Regional Comprehensive Cancer Center. All cases included were followed up for at least 2years, deaths from causes unrelated to TIPN were excluded. We report on the frequency and risk factors and establish a prognostic score of persistent Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9% developed persistent TIPN of grade 2 and 3, respectively. Two patients died from complications of grade 3 TIPN. Risk factors of persistent grade 2 and higher neuropathy included age (P<.0001), body mass index (P<.0001), and diabetes (P=.0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (OR=5.43; P<.0001). Patients presenting all four major risk factors had a 97.2% probability of developing long-term symptoms against 1.2% for patients showing no risk factor. We therefore identified 3 prognostic groups. TIPN is a frequent and sometimes severe persistent side effect of breast cancer treatment among elderly women with a major impact on health-related quality of life. Chemotherapy regimens without taxane could therefore be a valid option in elderly patients with neurotoxicity risk factors.

A three-dimensional modeling method for quantitative photoacoustic breast imaging with handheld probe

By providing complementary functional information, photoacoustic (PA) breast imaging based on the handheld ultrasound (US) probe has demonstrated promising potential for breast cancer diagnosis. However, the quantitative PA imaging primarily relies on the knowledge of the optical fluence distribution in the three-dimensional (3D) heterogeneous breast tissue. Previous studies based on the handheld system generally provided two-dimensional (2D) B-scan results, which contains limited anatomical information of the tissue and the lesion. This study proposed a method to perform 3D modeling of the photon transportation for dual-modality PA/US system based on the local 3D breast anatomical information by scanning US probe. Then the calculated optical fluence distribution can be used for PA imaging. Our phantom and clinical pilot study results demonstrated that this method has potential to improve the accuracy of the quantitative PA breast imaging, and it can also be used in other clinical implementations.

Autologous breast fibrofatty flaps for immediate breast reconstruction after excision of small cancer mass (&lt;50 mm) improves surgical and aesthetical outcomes and patients’ quality of life

Background: Evaluation of surgical feasibility, aesthetic outcomes and 6-m postoperative (PO) effect of immediate breast reconstruction (IBR) using autologous fibrofatty flaps after localized small breast mass excision.Methods: Total 29 women had duct carcinoma of &lt;50 mm in diameter with N1-3 regional lymphadenopathy were studied. Through diamond-shape incision, breast gland was removed with 1 cm circumferential free safety margin, then the medial and lateral fibrofatty flaps were undermined and approximated for IBR. Breast measurements; the nipple-to-suprasternal notch distance and the nipple-to-nipple distance were determined preoperatively and 6-m PO. Quality of life (QoL) evaluation was performed preoperatively and 6-m PO using the short-form-36 (SF-36), the multidimensional body self-relations questionnaire appearance assessment and the European organization for research and treatment of cancer breast cancer-specific QoL questionnaire scores in breast cancer. Results: Mean operative time was 94.5±15.4 min; mean intraoperative blood loss was 170.1±34.9 ml and 25 patients had returned home on the same operative day. Two patients had PO wound seroma and one patient had wound hematoma, but were resolved spontaneously. PO breast measurements showed non-significant differences in comparison to preoperative measurements of the same breast, and to measurements of the contralateral breast. PO evaluation of QoL showed significantly improved PO scoring in line with improved body image and future perspectives, and sexual scores in comparison to preoperative scorings. Conclusions: The applied procedure of localized excision of BC mass of&lt;50 mm with IBR using the breast remnant fibrofatty flaps provided acceptable surgical and esthetical outcomes and allowed improvement of patients’ QoL.

Factors that Influence Treatment Delay for Patients with Breast Cancer.

The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients. This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30days elapsed between biopsy and surgery. Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas. Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.

Role of supportive care in improving the quality of life and reducing unscheduled hospital care in patients with metastatic breast cancer.

Metastatic breast cancer (MBC) patients experience long survival and report poorer quality of life than localized breast cancer patients. Comprehensive supportive care (CSC) has been shown to improve the quality of life (QoL) of MBC. The respective part of each support care has not been fully examined, and little is known about whether meeting patients' needs is accompanied by decreased unscheduled hospital care (UHC). This prospective monocentric study included women who started a new treatment line for MBC between January 2018 and December 2018. The endpoints were factors associated with UHC and QoL (SF36) at month 12. 100 patients were offered CSC, 78 were included (21 refusals, 1 no MBC). CSC was provided to 60 patients: pain (43%), psychological (37%), kinesitherapy (30%), social assistance (22%), esthetic (18%), nutrition (18%), massage (13%), and none (10%). CSC rate was not statistically different among patients with (58%) and without UHD (49%). Factors associated with a decrease of UHC were age > 65 years (p = 0.01), no previous treatment for MBC (p = 0.0001) with a trend for the lack of CSC (p = 0.054). Among the 8 domains of the SF36 scale, only health change perception was improved (p = 0.01) and its predictive factors were treatment carried out as planned (p = 0.0004), pain care (p = 0.003), and lack of MBC progression (p = 0.0035). CSC can improve QoL in MBC. Painful patients might benefit more from CSC. UHC did not decrease for patients receiving CSC as expected possibly because of their important needs for clinical care.

Patient-Reported Outcomes and Frailty Among Participants in the NHLBI MDS Natural History Study

Introduction: Patient-reported outcomes (PROs) such as quality of life (QOL) are variably affected in patients with myelodysplastic syndromes (MDS), but the heterogeneous composition of disease states grouped together as "MDS" increases the difficulty of assessing and understanding these outcomes. Moreover, little is known about the potential relationship between QOL and frailty in this population. Methods: The NHLBI MDS Natural History Study (NCT02775383) is a prospective cohort enrolling patients undergoing diagnostic work up for suspected MDS or MDS/myeloproliferative neoplasms (MPNs) in the setting of cytopenias. Untreated participants undergo bone marrow assessment with centralized histopathology review at enrollment for assignment into subcategories for longitudinal follow-up: MDS, MDS/MPN, ICUS, AML (&amp;lt;30% blasts), and "At-Risk" (cases with sub-threshold dysplasia or select karyotypic or genetic mutations). PRO and frailty data are collected at enrollment and every six months thereafter. PRO instruments include MDS-specific (QUALMS) and general (FACT-G, PROMIS Fatigue Short Form 7a, EQ-5D-5L) instruments, and a measure of frailty (VES-13). While no frailty instrument alone has been shown to be a substitute for comprehensive geriatric assessment, VES-13 has been successfully used in cancer-related studies for basic screening, where a score of 3 or more is considered frail (vulnerable). An analysis of variance (ANOVA) was used for the overall comparisons of mean baseline scores between diagnostic categories. Pairwise comparisons of scores between diagnostic categories and vulnerability subgroups were performed via two-sample t-tests. Results : Of 835 participants assessed for eligibility, 369 (44%) were classified as MDS, MDS/MPN, AML, ICUS or At-Risk, and further evaluated. Mean age was 72 years (standard deviation (SD)=10.7) and 68% were male. Mean baseline scores on the PRO measures are compared between diagnostic categories in the Table; scores did not differ significantly across categories. In particular, no significant differences were found between MDS and the other diagnostic categories. ICUS had similar QOL scores to MDS and MDS/MPN (e.g., means (SD) on EQ-5D-5L of 74.1 (17.8) in ICUS and 70.8 (19.4) in MDS, p=0.348) but had significantly higher scores than those for AML on EQ-5D-5L (60.7 (28.4), p=0.031). For the 216 participants with diagnostically-confirmed MDS, QOL impairment was similar to that routinely seen in other cancers; for example, the mean total FACT-G was 81.8 (SD=15.9), similar to localized breast cancer (82.4, SD=16.2), localized colorectal cancer (79.6, SD=16.1), and lung cancer with no current evidence of disease (82.6, SD=15.5; comparison means from Pearlman, Cancer, 2014). For frail/vulnerable participants with MDS or MDS/MPN (N=87), the most common reasons for vulnerability were age ≥75 years (68%), overall rating of health as poor or fair (62%), and difficulty with prolonged physical activity (90%) such as walking a quarter mile (75%) or doing heavy housework (70%). A minority also were vulnerable due to requiring help with instrumental activities of daily living (iADLS) such as shopping (28%) or managing money (16%). Mean QOL scores were compared between vulnerability subgroups (Figure). Vulnerable participants pooled over all diagnostic categories had significantly worse PROs than non-vulnerable participants for all measures (p&amp;lt;0.001). In particular, vulnerable MDS participants scored significantly worse on the QUALMS (mean 64.4, SD=13.4) vs. non-vulnerable MDS participants (mean 72.7, SD=13.3), p&amp;lt;0.001. Conclusions: Participants in our cohort with histologically-confirmed MDS-even low-grade MDS-had similar impairments in PROs as those with other cancers. Among those with histologically-confirmed MDS, vulnerable participants had significantly worse QOL on many measures compared to non-vulnerable participants, suggesting that this domain of function be specifically assessed in clinic. Moreover, while a "gestalt" of frailty may be inferred by observing how patients present and move in the office, these data suggest that other contributing domains, such as difficulty with prolonged physical activity and iADLs, should be evaluated explicitly. Disclosures Foran: H3Biosciences: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Takeda: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Agios: Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Actinium: Research Funding; Aprea: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Trillium: Research Funding; Revolution Medicine: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding. Gore:Abbvie: Consultancy, Honoraria, Research Funding. Padron:Incyte: Research Funding; Kura: Research Funding; Novartis: Honoraria; BMS: Research Funding. Sekeres:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda/Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Two Rare Cases of Severe Autoimmune Dyserythropoiesis without Any Underlying Haematological Malignancy or Autoimmune Disease

Background: Autoimmune dyserythropoiesis is a rare disorder with only 4 adult cases and 3 paediatric cases reported in the literature. These suggest an underlying cause of haematological malignancy i.e. CLL or autoimmune disorder e.g. SLE1. Two proposed mechanisms of the pathophysiology include erythroblastic synartesis, or a Fas deficiency in autoimmune conditions2. There is no standard of care, however most cases respond to immunosuppression and/or treatment of the underlying condition. This is a report of 2 rare cases of severe autoimmune dyserythropoiesis without any underlying haematological or autoimmune conditions that have both responded to immunosuppression. Methods: Investigations included a haemolytic screen (LDH, bilirubin, haptoglobin, reticulocyte count and DAT), iron, B12 and folate studies, viral screening (EBV, CMV, HBV, HCV, HIV and parvovirus serologies and parvovirus PCR), autoimmune screen (ENA, ANA, RF, anti CCP, dsDNA, ANCA, C3/4), malignancy screen (EPG/IEPG and serum light chains, peripheral blood flow cytometry and imaging including CT CAP and/or PET scans). Bone marrow aspirate and trephine were performed with cytogenetics and molecular testing for myeloid mutations using NGS panels. Results: Case 1 is a 56-year-old female who initially presented in 2006 with fevers, weight loss, night sweats and an unexplained anaemia with a haemoglobin of 67g/L and MCV of 109 fl. WCC was 6.3 x10^9/L and platelet count 495 x 10^9/L. Clinical exam revealed no signs of haematological malignancy or autoimmune disease. Reticulocyte count was low at 7x10^9/L. ESR was significantly elevated at 130 mm/hr. Bone marrow biopsy was hypercellular with increased early erythroid precursors and some erythroid islands that resembled erythroblastic synartesis. Moderate dyserythropoiesis with numerous binucleate forms was also noted. The rest of her investigations were normal. She responded briskly to low dose prednisone (25mg daily) with resolution of her anaemia, reticulocytopaenia and inflammatory markers. She was transitioned onto azathioprine in 2011 as a steroid sparing agent which was ceased in 2018 due to a diagnosis of localised breast cancer. She remained in remission off immunosuppression for 18 months. Her relapse clinical findings and investigations were identical to her initial presentation. Her NGS testing at this time was negative for myeloid genetic mutations. She again responded briskly to prednisolone. Case 2 is a 65-year-old female referred for a 4th opinion in May 2019 regarding transfusion dependent anaemia. Clinical exam revealed no signs of malignancy nor autoimmune disease. Haemoglobin averaged 60g/L with a low reticulocyte count at 11x10^9/L and elevated MCV of 117fL. Ferritin was elevated secondary to multiple prior transfusions at 1190 ug/L. ESR and CRP were elevated with an ANA titre of 1:80 (homogenous). Bone marrow was hypercellular with some minor dysplastic features and increased immature forms. Peripheral blood flow cytometry revealed a small monoclonal B cell population (0.1% of lymphocytes) that was not detected on bone marrow biopsy. The rest of her investigations were normal. She declined a trial of steroid therapy She was commenced on weekly IV rituximab 375mg/m2 for 3 weeks but was unable to tolerate mild infusion reactions and had no response. She was then treated with intravenous immunoglobulin as well as iron chelation therapy and her anaemia, reticulocytopaenia and inflammatory markers quickly resolved. Discussion: These are two rare cases of severe autoimmune dyserythropoiesis with reticulocytopaenia with no autoimmune haemolysis and no underlying autoimmune or malignant disease. Due to the rarity of this disease, there are no clear guidelines on how to manage these patients and more evidence/research is required. Both cases responded well to immunosuppressive treatment in a relapsing/remitting fashion that further reinforces the autoimmune nature of this disease.One patient did not respond to rituximab despite a small monoclonal B lymphocyte population unlike the only other case treated with rituximab reported where this was successful.

Long term continuous Trastuzumab use for HER2-positive advanced breast cancer

Objectives: Trastuzumab is the standard of care for locally advanced / metastatic her2-positive breast cancer. However, most of these patients will progress within 12 months of trastuzumab therapy. In contrast, there is a paucity of data available on the long-term treatment of patients with Trastuzumab. Our study was conducted to report efficacy and safety data for patients with locally recurrent / metastatic her2-positive breast cancer who received long-term therapy with Trastuzumab (≥5 years).&#x0D; Methods: This study was a prospective single-arm study of continuous Trastuzumab in patients who were histologically her2-positive and radiologically confirmed inoperable locally recurrent or metastatic breast cancer after complete one year of Trastuzumab plus chemotherapy (in hormone negative/hormone resistance) treatment then continuous Trastuzumab alone , or with hormone therapy (in sensitive hormone positive) without progression [complete or partial response or stable disease]. A total of 50 inoperable local recurrent and metastatic breast cancer patients were treated with continuous intravenous Trastuzumab therapy administered according to the standard Trastuzumab every 3-weeks (8 mg/kg loading dose followed by 3-weekly 6 mg/kg maintenance doses starting 3 weeks after the loading dose) schedule, from January 2014 to January 2019 at the Najaf Cancer Clinic (NCC).&#x0D; Results: All 50 patients were evaluated with CR occur only in 20% (10/50) with an OAR of 50% (25/50). The cardiac status of these patients remained stable over time for the majority of patients with no marked changes in LVEF%. No treatment-related death was observed. The median OS and median PFS is 61 months and 20 months, respectively.&#x0D; Conclusion: In her2-positive recurrent and metastatic breast cancer patients, who initially respond to palliative treatment with trastuzumab, continuous trastuzumab can achieve a long-term tumor remission of several years and had significantly improved survival with tolerated and acceptable adverse events.

Polycyclic organic matter and invasive breast cancer

p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px 'Helvetica Neue'} Background: Emerging evidence suggests that environmental endocrine disrupting chemicals, such as polycyclic aromatic hydrocarbons (PAHs), increase breast cancer risk. Polycyclic organic matter (PAHPOM) is a USEPA Environmental Quality Index (EQI) air domain factor, which includes PAHs and PAH-derivatives present in the atmosphere in particulate form. Sources include tobacco smoke, vehicle exhaust, residential heating, coal and tar burning, and grilling meat. Methods: Herein, we investigated associations between polycyclic organic matter exposure and invasive breast cancer. Breast cancer diagnoses were obtained from the North Carolina Central Cancer Registry (2009-2014), and county of residence at diagnosis was linked with the quartiled PAHPOM variable. We first constructed generalized linear models to assess county-level breast cancer incidence by stage in counties of high versus low PAHPOM exposure, adjusted for mammography screening rates, %African American, and %Smokers. Next, we constructed generalized estimating equations to evaluate the odds of individual patients having localized, regional, or distant invasive breast cancer versus non-invasive carcinoma in situ in counties of high versus low PAHPOM exposure, adjusted for age, BMI, smoking status, and race. We further evaluated the odds of patients having hormone receptor positive versus hormone receptor negative invasive breast cancer. All models were stratified by urbanicity. Results: High PAHPOM exposure was associated with increased total and localized breast cancer incidence (total estimate 22.36, 95% CI 6.77-37.95, p=0.006; localized estimate 12.43, 95% CI 3.36-21.5, p=0.008), as well as increased odds of having hormone receptor positive versus hormone receptor negative invasive breast cancer (OR 1.04; 95% CI: 1.00, 1.08, p=0.0187) in urban counties. Conclusions: Our results suggest that high polycyclic aromatic compound exposure is associated not only with increased breast cancer incidence, but also increased odds of having hormone receptor positive invasive breast cancer, especially in urban areas.

Dose-Weighted CT Radiomics Associated with Radiation-Induced Cardiac Toxicity in Women Treated for Localized Breast Cancer

Breast cancer continues to be the most commonly occurring non-skin cancer in women. Survivorship is of increased importance as women are living longer after treatment. Cardiac toxicity after radiotherapy (RT) is a concern for such patients who otherwise have excellent life expectancy. We hypothesize via this exploratory analysis that dose-weighted texture features from pre-treatment CT may predict for cardiac toxicity post-RT for women with breast cancer. We retrospectively analyzed 17 patients treated with standard RT for localized breast cancer between 2011-2016 at a single institution. Patients had no known heart disease pre-RT. Eight patients with cardiac disease post-RT, diagnosed via echocardiogram or cardiac catheterization, were compared to 9 patients without cardiac disease post-RT. Using published contouring guidelines, each treatment planning CT was used for delineation of the heart, cardiac chambers, left main coronary artery, left anterior descending coronary artery, left circumflex artery (LCX), right coronary artery, atrioventricular (AV) node, ascending aorta and pulmonary artery. Ninety-two geometric, first-, second-, and third-order conventional texture features were extracted for each structure. An in-house developed software modified the features by dose weighting on a voxel-by-voxel basis, resulting in an additional 65 dose-weighted textures. Random forest was used for analyses. A univariate logistic regression model was used to estimate odds ratio (OR) and p-value for each imaging feature – with and without dose weighting. Eight patients were diagnosed with pericarditis (n = 1), arrhythmia (n = 1), coronary artery disease (n = 2), or heart failure (n = 4) a median of 3 years after completion of RT (mean: 3.5 years). RT was delivered to the left breast (n = 4), left chest wall (CW, n = 2), and right CW (n = 2) with mean heart dose of 2.1 Gy (range: 0.4-5.25 Gy). The 9 reference patients without cardiac sequelae were treated with RT to the left chest wall with mean heart dose of 2.7 Gy (range: 1.4-6.8 Gy). On univariate analysis, left atrium volume (OR: 39.89, p = 0.04) and a dose-weighted feature of the right ventricle (OR: 0.15, p = 0.03) were significantly associated with cardiac disease. Several dose-weighted texture features approached significance including those of the AV node (OR: 42.37, p = 0.08), left atrium (OR 0.10, p = 0.07), LCX (OR:8.5, p 0.09), and right atrium (OR:8.5, p = 0.09). Area under the receiver operating characteristic curve (AUC) ranged between 0.75 and 0.88. Dose-weighted texture features of the right ventricle and left atrium volume were significantly associated with development of cardiac disease post-RT. Multiple dose-weighted features approached significance, suggesting that distribution of dose amongst subsites may affect cardiac outcomes. Future directions include expansion of the database by cardiac disease type with covariate analysis including systemic therapy and comorbidities.

Factors influencing psychological wellbeing of early breast cancer patients.

This paper aims to identify factors that influence the psychological wellbeing of patients newly diagnosed with localized breast cancer. Psychological wellbeing plays a significant part in the personal experience of patients during their cancer journey. However, despite progress in treatments and outcomes in breast cancer, psychosocial services and emotional support of cancer patients have been given less attention. Data were collected through a retrospective review of 274 charts of women diagnosed with breast cancer between 2012 and 2017 that received care in a single cancer center. Disease specific parameters, social and demographic variables, and Edmonton Symptom Assessment System (ESAS) scores were extracted from the patient charts. Self-reported scores of psychological-related symptoms were low (suggesting no or minimal psychological distress) at baseline and remained low in the majority of patients with breast cancer. Pain, depression, anxiety and wellbeing scores of 0-2 were observed in 78.5%, 81.4%, 63.5% and 70.1% of patients, respectively. Higher scores of anxiety at baseline were observed in patients with physical restrictions on the Eastern Cooperative Oncology Group performance status (ECOG PS) (14.9%), current smoking (20.5%) and history of mental illness (19.1%). Increasing scores for pain were observed in older patients during treatment as compared to baseline. Mastectomy was associated with increased scores for wellbeing (worsening wellbeing) as compared to lumpectomy. Of the patients with a history of mental illness (17.3%), 19.1% had more often increased scores for anxiety. The findings highlight patients that may benefit from additional social and psychological supports at diagnosis and while undergoing treatment.

235 Poster - Pyrotinib in HER2-Positive local advanced or metastatic breast cancer patients: Results from a retrospective study in real-world setting

235 Poster - Pyrotinib in HER2-Positive local advanced or metastatic breast cancer patients: Results from a retrospective study in real-world setting

S1616 A Nonspecific Gastrointestinal Symptom Leads to a Rare Colonic Metastasis in a Patient With Remote History of Breast Cancer

INTRODUCTION: Breast cancer is the second most common malignancy in women and can metastasize to the lungs, bone, and liver; colonic metastases are exceedingly rare. We discuss a breast cancer survivor who presented with non-specific GI symptoms and was found to have metastatic breast cancer in the colon. CASE DESCRIPTION/METHODS: This is a 74-year-old female with a remote history of localized right breast cancer initially managed with breast-conserving surgery and radiation in the late 1980s, then maintained on an estrogen receptor (ER) antagonist before receiving a mastectomy in the late 1990s. She adhered to mammogram surveillance that confirmed her remission for the following two decades. At our clinic, she complained of decreased stool caliber and constipation refractory to over-the-counter laxatives. Symptoms were present for four weeks, associated with nausea, and without weight loss, abdominal pain, or blood in stool. She was up-to-date with colonoscopies. Exam revealed a soft abdomen with a firm focus near the umbilicus without tenderness on palpation. Colonoscopy revealed a region of erythematous friable mucosa with ulcerations at the transverse colon measuring 3 cm wide (Figure 1A). Pathology revealed a poorly differentiated carcinoma and GATA3, a breast carcinoma marker, was strongly positive (Figure 1B/D). E-cadherin was negative indicating this is most likely lobular carcinoma and ER, progesterone receptor, and HER-2 were all negative. Subsequent imaging confirmed metastases to the colon and retroperitoneum. She established care with oncology and has since been initiated on chemotherapy. DISCUSSION: Breast cancer metastases to the colon are a rare finding. The frequency at which metastases occur and the time at which they present depends on histologic subtype and hormone receptor status, respectively. Lobular carcinomas, as in our patient, tend to metastasize more than other subtypes. Also, hormone receptor-negative disease tends to metastasize earlier than hormone receptor-positive disease, with the former typically appearing within five years after initial diagnosis and the latter presenting well beyond that. Although our patient has lobular carcinoma, she also has triple-negative disease confirming exceptions to these rules. We present this case not only to highlight an atypical presentation of a common malignancy but to emphasize that providers should maintain a high index of suspicion for cancer recurrence when evaluating nonspecific gastrointestinal complaints in cancer survivors.Figure 1.: A. Endoscopic view of transverse colon demonstrating erythematous friable mucosa with ulceration. Ulcer measures three centimeters wide. B. Hematoxylin and Eosin stain: Ulcerated mucosa with underlying dense infiltrate of poorly differentiated neoplastic cells in the lamina propria. Of note, non-neoplastic colonic mucosa with unremarkable colonic glands/crypts are seen on the left of the dotted red line (arrow). C. Immunohistochemistry for CDX2. The neoplastic cells are negative for CDX-2, ruling out the possibility of adenocarcinoma of the GI tract. D. Immunohistochemistry for GATA 3. The neoplastic cells are positive for GATA3, suggesting breast origin of these neoplastic cells.

Environmental Quality and Invasive Breast Cancer.

Background: Breast cancer is a complex and multifactorial disease, and environmental factors have been suggested to increase its risk. However, prior research has largely focused on studying exposures to one factor/contaminant at a time, which does not reflect the real-world environment.Methods: Herein, we investigate associations between breast cancer and the environmental quality index (EQI), a comprehensive assessment of five domains of environmental quality (air, water, land, sociodemographic, and built environments) at the county level. Breast cancer diagnoses for North Carolina women were obtained from the North Carolina Central Cancer Registry (2009-2014) and the county of residence at the time of diagnosis was linked with the EQI. We evaluated the odds of localized, regional, or distant metastatic breast cancer in categories of environmental quality using women with carcinoma in situ as registry-based controls.Results: Overall environmental quality was generally not associated with invasive breast cancer; however, all breast cancer types tended to be inversely associated with land quality, particularly in more rural communities [distant metastatic breast cancer was 5%-8% more likely (OR, 1.08; 95% confidence interval, 1.02-1.14; P = 0.02) compared with carcinoma in situ].Conclusions: Cumulatively, our results suggest that some broad measures of environmental quality are associated with invasive breast cancer but that associations vary by environmental domain, cancer stage, subtype, and urbanicity.Impact: Our findings suggest that components of land quality (e.g., pesticide applications and animal facilities) warrant additional investigation in relation to invasive breast cancer.See all articles in this CEBP Focus section, "Environmental Carcinogenesis: Pathways to Prevention."

13 Oral - Safety of pre-pectoral breast reconstruction followed by post mastectomy radiotherapy

Background: Implant-based breast reconstruction (IBBR) after mastectomy either with TE or DTI in pre-pectoral position has been widely accepted. The pre-pec breast reconstruction, in fact, spares muscles, preserving the natural anatomy and reduces post-operative pain. Moreover, the pre-pec approach is associated to a decreased risk of capsular contracture and animation deformities. An increasing number of women, who undergo IBBR, will require post mastectomy radiotherapy (PMRT), since the meta-analysis of Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) confirmed a significant reduction of both local recurrence and breast cancer mortality in patients with pathological nodal involvement and locally advanced cancer.

Metastasis: A Bane of Breast Cancer Therapy

The underlying mechanisms of metastasis in patients with breast cancer is still poorly understood. Approximately 6% of patients with breast cancer present with metastasis at the time of diagnosis. Metastatic breast cancer is difficult to treat and patients with breast cancer with distant metastasis have a significantly lower 5-year survival rate compared to patients with localised breast cancer (27% and 99%, respectively). During breast cancer progression, tumour cells first metastasise to nearby draining lymph nodes and then to distant organs, primarily bone, lungs, liver, and brain. In this brief review, the authors discuss breast cancer metastasis, the role of epithelial–mesenchymal transition and the contributions of the immune system to the metastatic process. The authors also briefly discuss whether there is any relationship between tumour size and metastatic potential, and recent advances in treatment for metastatic breast cancer. The studies highlighted suggest that immunotherapy may play a more significant role in future patient care for metastatic breast cancer.

Studying Adipose Tissue in the Breast Tumor Microenvironment In Vitro: Progress and Opportunities.

The breast cancer microenvironment contains a variety of stromal cells that are widely implicated in worse patient outcomes. While many in vitro models of the breast tumor microenvironment have been published, only a small fraction of these feature adipocytes. Adipocytes are a cell type increasingly recognized to have complex functions in breast cancer. In this review, we examine findings from recent examples of in vitro experiments modeling adipocytes within the local breast tumor microenvironment. Both two-dimensional and three-dimensional models of adipocytes in the breast tumor microenvironment are covered in this review and both have uncovered interesting phenomena related to breast tumor progression. Certain aspects of breast cancer and associated adipocyte biology: extracellular matrix effects, cell-cell contact, and physiological mass transport can only be examined with a three-dimensional culture platform. Opportunities remain for innovative improvements to be made to in vitro models that further increase what is known about adipocytes during breast cancer progression.

Cognitive Impairment in Patients with Breast Cancer before Surgery: Results from a CANTO Cohort Subgroup.

Twenty to 30% of patients with breast cancer have cognitive impairment after surgery and before adjuvant treatment, but very few studies have focused on cognition before any treatment. This study used a subgroup of women with newly diagnosed breast cancer from the French cancer and toxicities (CANTO) cohort to describe cognition before any treatment in comparison with a group of healthy controls (HC). Cognitive assessment was performed before any breast cancer treatment (surgery or neoadjuvant treatment) on women with newly diagnosed invasive stage I-III breast cancer and HCs. Objective cognitive performance, cognitive complaints, anxiety, depression, and fatigue were assessed. Objective cognitive impairment was defined according to International Cognition and Cancer Task Force recommendations. Of the 264 included patients with breast cancer (54 ± 11 years) and 132 age-matched HCs (53 ± 9 years), overall objective cognitive impairment was observed in 28% of patients with breast cancer and 8% of HCs (P < 0.001). Cognitive complaints were reported by 24% of patients versus 12% of HCs (P < 0.01). Patients reported significantly more anxiety and emotional and cognitive fatigue than HCs (P < 0.01). After adjustment, significantly more patients with breast cancer had overall objective cognitive impairment than HCs [OR = 3.01; 95% confidence interval (CI): 1.31-6.88] without significant difference between groups for cognitive complaints (OR = 1.38; 95% CI: 0.65-2.92). Cognitive complaints were positively associated with fatigue (OR = 1.03; 95% CI: 1.02-1.05). In this prospective study, compared with HCs, patients with localized breast cancer had more objective cognitive impairment before any treatment. Cognitive complaints were mostly related to fatigue. Baseline assessment before treatment is important to assess the impact of each cancer treatment on cognition.

Abstract A09: Predicting recurrence or second breast cancer using linked claims and cancer registry data with limited gold-standard information: A gradient-boosting approach

Abstract Background: Cancer recurrence is a major event affecting the burden of the disease and is a critical decision point for patients and their providers. Population-based information on the risk of cancer recurrence is lacking because it is not routinely collected by cancer registries. Objective: To develop and implement a scalable, supervised learning algorithm to predict breast cancer recurrence status using information about disease at diagnosis from registry data and information about health care utilization from medical claims. Data: Medical claims from private insurers and Medicare (2011-2016) linked with the Puget Sound SEER Cancer Registry were made available via the Hutch Institute for Cancer Outcomes Research (HICOR). Gold-standard information on the recurrence of initially localized breast cancer was provided by investigators on the BRAVO study of breast cancer survivors diagnosed 2004-2016 in the Puget Sound area. The HICOR and BRAVO data were linked. The analysis dataset consisted of 111 patients with a recurrence or second breast cancer event and 689 patients without a recurrence or second breast cancer event who had adequate claims (insurance enrollment before and after their second event or for at least 12 consecutive months after primary treatment) available for analysis. Methods: A gradient-boosting algorithm (XGBoost) was harnessed to predict month-level recurrence status, i.e., whether any given month was before or after a recurrence event. Features included registry information on patient demographics, initial extent of disease, and hormone-receptor, and engineered features based on the counts of diagnosis, procedure and drug claims within groups determined by a blend of previously defined groups and groups customized for this application. Time-varying features included monthly counts of codes within each group, months since the most recent and subsequent occurrence of each code group, and cumulative sums of each code group. Subjects were split into a training (n=94) and test (n=17) set for reporting performance results. The training data were further split 5:1 for cross-validation purposes. Results: The list of most important variables included time since coding of secondary malignancy, cumulative sum of codes related to pathology, and codes related to catheter placement. The month-specific AUC on a validation subset (n=17 patients) was 0.89; individual-level (sensitivity, specificity) ranged from (0.824, 0.946) to (0.706,0.982). Conclusions: Data sources that link claims, cancer registry, and gold-standard disease status information are critical for the development of novel, automated approaches for detecting cancer recurrence. Gradient-boosted learning with engineered time-varying features shows promise for identifying recurrence events in administrative claims. Proper coding of procedure and drug groups is likely to be key to the performance of such algorithms. Incompleteness of claims data is a major challenge. Citation Format: Teresa A'mar, Daniel Markowitz, Jessica Chubak, David Beatty, Catherine Fedorenko, Christopher Li, Kathi Malone, Ruth Etzioni. Predicting recurrence or second breast cancer using linked claims and cancer registry data with limited gold-standard information: A gradient-boosting approach [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A09.

Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells.

Despite the leaps and bounds in achieving success in the management and treatment of breast cancers through surgery, chemotherapy, and radiotherapy, breast cancer remains the most frequently occurring cancer in women and the most common cause of cancer-related deaths among women. Systemic therapeutic approaches, such as chemotherapy, although beneficial in treating and curing breast cancer subjects with localized breast tumors, tend to fail in metastatic cases of the disease due to (a) an acquired resistance to the chemotherapeutic drug and (b) the development of intrinsic resistance to therapy. The existence of cancer stem cells (CSCs) plays a crucial role in both acquired and intrinsic chemoresistance. CSCs are less abundant than terminally differentiated cancer cells and confer chemoresistance through a unique altered metabolism and capability to evade the immune response system. Furthermore, CSCs possess active DNA repair systems, transporters that support multidrug resistance (MDR), advanced detoxification processes, and the ability to self-renew and differentiate into tumor progenitor cells, thereby supporting cancer invasion, metastasis, and recurrence/relapse. Hence, current research is focusing on targeting CSCs to overcome resistance and improve the efficacy of the treatment and management of breast cancer. Studies revealed that metformin (1, 1-dimethylbiguanide), a widely used anti-hyperglycemic agent, sensitizes tumor response to various chemotherapeutic drugs. Metformin selectively targets CSCs and improves the hypoxic microenvironment, suppresses the tumor metastasis and inflammation, as well as regulates the metabolic programming, induces apoptosis, and reverses epithelial–mesenchymal transition and MDR. Here, we discuss cancer (breast cancer) and chemoresistance, the molecular mechanisms of chemoresistance in breast cancers, and metformin as a chemo-sensitizing/re-sensitizing agent, with a particular focus on breast CSCs as a critical contributing factor to acquired and intrinsic chemoresistance. The review outlines the prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer/chemo-sensitizing drug in the treatment of breast cancer. It intends to provide a rationale for the use of metformin as a combinatory therapy in a clinical setting.