bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PD5-02: Dcis as a risk lesion for invasive breast cancer and death from other cancers
Authors: Thompson Alastair , Hilton Bridget , Dulson-Cox Joanna , Clements Karen ,   Sloane Project NHS Breast Screening Group
Published: February 2021

Introduction: Ductal carcinoma in situ (DCIS) is considered a non-obligatory precursor of invasive breast cancer. Using a prospective cohort study of screen detected non-invasive neoplasia from a national breast screening program, this analysis examined subsequent DCIS or invasive cancers and death due to other cancers or other causes. Methods: Prospective data on 9191 screen detected non-invasive breast neoplasia with a median 9.2 years follow up was matched to a subsequent diagnosis of invasive breast cancer or death from another primary, non-breast cancer at any site or other cause of death, cross validating data from the National Cancer Registry, Hospital Episode Statistics and mortality data.

Results: Following a diagnosis of screen detected DCIS, in 9191 women, for those undergoing breast conservation surgery (BCS), 413 women developed ipsilateral invasive breast cancer, at a proportion of 5/1000 per annum consistent over a decade and more. By contrast DCIS re-occurances in the same, conserved, breast (in 222 women) occurred at a similar rate for the first 5 years then the rate halved beyond 5 years. Contralateral breast cancer (DCIS or invasive) occurred in 431 women over the same time period. Mortality occurred in 1062/9191 (11.6%) women, attributed to breast cancer in 130/1062 (12.2%) and due to cancer at other sites in 397/1062 (37.4%). Death from other, non-breast, cancers was predominantly from primaries of the lung (98 women), ovary (43), pancreas (37) and colon (23) and rarely associated with a confounding diagnosis of invasive breast cancer (present in only 8% of those patients). Non-cancer mortality was identified in 496/1062 (46.7%) women, most commonly attributed to cardiovascular disease (in 188 women) or disease of the respiratory system (in 93). Conclusion: Screen detected DCIS is a marker for subsequent invasive breast cancer, but mortality from other, non-breast, cancers following treatment for DCIS is three times more likely than death due to breast cancer, suggesting DCIS is a more general marker for subsequent cancers than hitherto recognized. Awareness of, and potentially screening for, other cancers should be considered in women treated for DCIS.

Citation Format: Alastair Thompson, Bridget Hilton, Joanna Dulson-Cox, Karen Clements, Sloane Project NHS Breast Screening Group. Dcis as a risk lesion for invasive breast cancer and death from other cancers [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-02.
Abstract PS1-26: Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study
Authors: Cabioglu Neslihan , Karanlık Hasan , Muslumanoglu Mahmut , Karadeniz Çakmak Guldeniz , Trablus Didem Can , Tukenmez Mustafa , Ersoy Yeliz E. , Uras Cihan , Zengel Baha , Emiroğlu Selman , Polat Ayfer Kamalı , Yeniay Levent , Ozkurt Enver , Kara Halil , Ibis Kamuran , Aydiner Adnan , Ozmen Vahit , Igci Abdullah
Published: February 2021

BACKGROUND: Omitting axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC) is still controversial. In this study, we evaluated factors affecting local recurrence and outcome in patients with LABC, who underwent SLNB alone after NAC. METHODS: Between 2004 to 2018, 320 patients with clinically node-positive LABC who received NAC and underwent SLNB alone after negative axillary staging were analyzed. All patients had breast and/or regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 228 patients had ypN0 disease (71.25%), whereas 92 patients had ypN(+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastasis (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 37 months (24-172), one patient (0.3%) with macrometastatic SLN having extracapsular extension was found to have locoregional recurrence at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found as 87% and 95%, respectively. Patients with cT3&4 (HR=2.22, 95% CI; 1.07-4.62), non-luminal molecular pathology (HR=2.71, 95% CI, 1.23-5.97), and non-pCR in the breast (HR=2.21, 95% CI, 0.94-5.17) were found to have an increased HR compared to others in 5-year DFS. However, no significant differences could be found between patients ypN0, ypN-ITCµmetastasis and ypN-macrometastasis regarding 5-year DFS and DSS rates. CONCLUSIONS: ALND could be safely avoided in selected patients with LABC who underwent SLNB after NAC having cT1-2, luminal pathology, breast and/or nodal pCR or low volume nodal disease, as long as axillary radiotherapy is provided.

Citation Format: Neslihan Cabioglu, Hasan Karanlık, Mahmut Muslumanoglu, Guldeniz Karadeniz Çakmak, Didem Can Trablus, Mustafa Tukenmez, Yeliz E. Ersoy, Cihan Uras, Baha Zengel, Selman Emiroğlu, Ayfer Kamalı Polat, Levent Yeniay, Enver Ozkurt, Halil Kara, Kamuran Ibis, Adnan Aydiner, Vahit Ozmen, Abdullah Igci. Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-26.
Abstract PS1-50: Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis
Authors: Reinhorn Daniel Jack , Mutai Raz , Yerushalmi Rinat , Moore Assaf , Amir Eitan , Goldvaser Hadar
Published: February 2021

Background: De novo metastatic breast cancer represents around 6% of breast cancer diagnoses. Retrospective data suggest that locoregional therapy (LRT) for the primary breast cancer in metastatic disease may improve outcomes. Randomized control trials (RCTs) have evaluated the role of LRT in this setting with inconsistent results. Methods: We searched PubMed to identify RCTs that compared LRT and standard systemic therapy to standard therapy alone in de novo metastatic breast cancer. The search was supplemented by a review of abstracts from key conferences. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) data were extracted for the intention to treat (ITT) population and for pre-specified subgroups defined by tumor subtype and by site of metastases. Subgroup analysis evaluated the effect of systemic treatment prior randomization to LRT. Results: Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was mandatory in 3 studies. Systemic treatment prior randomization showed similar results (HR=0.92 and HR=1.06 for upfront LRT and LRT following systemic treatment, respectively, p for the subgroup difference=0.72). LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p=0.81). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR for OS= 0.96, 95% CI 0.65-1.43, p=0.85), triple negative (HR 1.4, 95% CI 0.50-3.91, p=0.52) and human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.93, 95% CI 0.68-1.28, p=0.67). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62, p=0.92) and in visceral disease (HR=1.02, 95% CI 0.77-1.35, p=0.90). Conclusions: LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups.

Citation Format: Daniel Jack Reinhorn, Raz Mutai, Rinat Yerushalmi, Assaf Moore, Eitan Amir, Hadar Goldvaser. Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-50.
Abstract PS1-51: A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery
Authors: Kang Young-Joon
Published: February 2021

Introduction Focus has moved to de-escalate of axillary surgery in the management of early breast cancer. Based on the American College of Surgeons Oncology Group-Z0011, our team created the nomogram to be useful for identifying patients who do not require intraoperative analysis of the sentinel lymph node. The nomogram could identify as patients likely to three or more positive axillary lymph nodes by preoperative imaging. But the nomogram had several limitations. This study investigated a developed nomogram by excluding the chest computed tomography (CT) and adding 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT as a modality. Material and Methods Patients underwent preoperative ultrasonography (US) and PET/CT. The training set consisted of 1030 patients with clinical T1-2 and node-negative invasive breast cancer. Factors associated with ≥ 3 involved axillary lymph nodes (ALNs) were evaluated by logistic regression analysis. The validation set consisted of 781 independent patients. The nomogram was applied to 1,067 patients who met the selection criteria of the ACOSOG-Z0011. Results Of the 1,030 patients, 89 (8.6%) had ≥ 3 positive nodes. Multivariate analysis according to be used for making a new nomogram to predict the probability of involvement ≥ 3 nodes, there was significantly associated with larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT. The areas under the receiver operating characteristic curve of the nomogram were 0.856 (95% confidence interval [CI], 0.815 to 0.897) for the training set and 0.866 (95% CI, 0.799 to 0.934) for the validation set. Application of the nomogram to the patients who met the ACOSOG-Z0011 showed that 90/1067 (8.4%) had scores above the cut-off and the false-negative rate was 37/977 (3.8%). And the specificity was 93.8%, and the negative predictive value was 96.4%. Conclusion The upgraded nomogram improved predictive accuracy, and that was possible using only US and PET/CT. It reduced operation time and cost, with a very low re-operation rate. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes.

Citation Format: Young-Joon Kang. A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-51.
Abstract PS1-54: Risk factors for lymph node metastasis and the role of SLNB in microinvasive breast cancer
Authors: Paik Pill Sun , Cho Min Kyung , Ahn Juneyoung , Yoon Chang Ik , Yoo Tae-Kyung , Park Woo-Chan
Published: February 2021

Introduction Incidence of microinvasive Breast cancer (DCISM) along with ductal carcinoma in situ is increasing due to mammographic screening. However, DCISM is not a common pathologic entity and surgical management of the axilla, overall treatment, and prognosis of this entity still remains unclear. Our study aims to determine whether sentinel lymph node biopsy (SLNB) is necessary for all DCISM patients and analyze the characteristics of lymph node-positive patients among DCISM patients to identify risk factors associated with lymph node metastasis. Materials and MethodsA total of 184,007 Breast cancer patients treated were registered in the Korean Breast Cancer Society Registry between 1978 to 2020. A retrospective review of the database was performed and the analysis includes diagnostic and clinic-pathologic characteristics such as positive lymph node and immunohistochemistry. A univariate analysis was carried out to determine associations between lymph node positivity and the clinical variables via Fisher’s exact test.ResultsOf the 184,007 patients, 2,556 (1.4%) breast cancer patients were classified as DCISM and 134 (5.2%) had at least one lymph node (node-positive), while 2,422 were node-negative patients. We found statistically significant results with hormone receptor status between node-positive and node-negative patients. Estrogen receptor (ER) and progesterone receptor (PR)-negative cases were associated with lower ORs (ER: OR=0.63, 95CI=0.43-0.92, P=0.016; PR: 0.67, 0.46-0.96, 0.026, respectively). A particularly interesting finding is that human epidermal growth factor receptor 2 (HER2)-negative cases were associated with higher OR (HER2: 2.03, 1.36-3.06, 0.001), suggesting hormone receptor status could be useful to identify potential lymph node metastases.ConclusionOur study suggests that we could omit axillary staging in DCISM patients, and consider optional SLNB in patients with ER, PR, and HER2 status with other overrepresented clinical entities such as palpable mass, BMI, and histologic grade.KeywordsMicroinvasive ductal carcinoma, Sentinel lymph node biopsy, lymph node metastasis

Citation Format: Pill Sun Paik, Min Kyung Cho, Juneyoung Ahn, Chang Ik Yoon, Tae-Kyung Yoo, Woo-Chan Park. Risk factors for lymph node metastasis and the role of SLNB in microinvasive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-54.
Abstract PS1-57: Mastectomy versus breast conserving surgery for the management of locally advanced breast cancer
Authors: Arora Roochi , Kazemi Ghazaleh , Lucas Graydon
Published: February 2021

Background: Breast conserving surgery (BCS) has become increasingly employed as a surgical option for patients with locally advanced breast cancer (LABC). However, guidelines on selecting appropriate LABC patients for BCS remain vague. Methods: Our Local Integrated Health Network (LHIN) conducted a multidisciplinary conference, known as the LHIN4 day, during which consensus criteria on which LABC patients may be safely offered BCS were established. These criteria included: clinical T3 or smaller, clinical and/or radiographic response to neoadjuvant therapy, patient seen by radiation oncology and deemed a candidate for post-operative radiation, and surgeon confident that negative margins could be achieved. A retrospective chart review was then performed of patients treated with neoadjuvant systemic therapy for LABC in the one year before, and three years after the LHIN4 day, which was between June 2015 and June 2019. Objectives: The primary objective of this study was to determine the rates of local and distant breast cancer recurrence in LABC patients treated with BCS using our consensus guidelines. The secondary objectives were: (1) to determine if there was an increase in BCS being performed following the LHIN4 educational day as compared to before this day, (2) to determine the rates of mastectomy followed by reconstruction among the patients treated within the past 3 years, and (3) to determine the rates of pathologic complete response (PCR). Results: A total of 391 patients were included in this study. Among the 26 patients who underwent BCS, the rate of local recurrence was 0% (0/26), and the rate of distant recurrence was 12% (3/26). Rates of BCS were 1.9% (2/108) before the LHIN4 day, and 8.5% (24/283) after the LHIN4 day. Rates of mastectomy followed by reconstruction were 12% (21/181) in the last 3 years. PCR was achieved in 15% (58/391) of all patients, of which 57% (33/58) were Her2 positive and 24% (14/58) were triple negative. Conclusion: We propose specific criteria for appropriately selecting LABC patients for BCS. Our results indicate that these criteria can be feasibly applied with low rates of local and distant breast cancer recurrence. A minority of patients with LABC who do not undergo BCS, either due to ineligibility or personal preference, are opting for mastectomy with reconstruction.

Citation Format: Roochi Arora, Ghazaleh Kazemi, Graydon Lucas. Mastectomy versus breast conserving surgery for the management of locally advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-57.
Abstract PS1-65: What lessons can be learned from the poly implant prothese scandal ? A french retrospective study
Authors: Pauly Lea , Couturaud Benoit , Reyal Fabien
Published: February 2021

Background : Silicone breast implants from the French manufacturer Poly Implant Prothese (PIP) were recalled from the French market after the use of a non-medical silicone filler has been established. The systematic explantation of the implants had been proposed to women with PIP implants in France, a preventive measure concerning approximately 30,000 patients.Objectives : This study aimed to evaluate the consequences of having at least one PIP breast implant on overall and disease-free survival after breast reconstruction for cancer or prophylactic surgery.Materials and Methods : We performed a multicentric retrospective cohort study on women who underwent immediate or delayed implant-based reconstruction after curative or prophylactic mastectomy between January 01,2002 and March 30,2010 in three French private health institutions of public interest. These dates correspond respectively to the arrival of PIP breast implants on the French market and the decision to withdraw them by the French government. The primary endpoints were disease-free and overall survival, depending on whether or not having a PIP breast implant used during breast reconstruction of prophylactic surgery.Results : We identified 2499 patients with the use of 4106 breast implants between 2002 and 2010.The median age of cancer diagnosis was 47 years (19-77). This patient population selected for breast reconstruction had good prognosis criteria (77% T1 and 68% N0). PIP was the most common brand used between 2002 and 2010 and represented 45% of all breast implants (1764 implants). PIP has been preferentially used in courses with immediate breast reconstruction. On the 1764 PIP, 1408 (80%) were removed, mainly after the preventive measure recommending systematic explantation. Censored data on March 30, 2010, showed that the incidence of PIP implants removal is lower than other brands (Log-rank test : p<0.001). Overall survival of patients who had at least on PIP was no different from that of patients who never had a PIP (Log-rank test : p=0.2). Disease-free survival was also similar between these two populations (Log-rank test : p=0.12).Conclusion : We did not identify any increase in local-regional recurrence or overall mortality associated with the use of PIP.

Citation Format: Lea Pauly, Benoit Couturaud, Fabien Reyal. What lessons can be learned from the poly implant prothese scandal ? A french retrospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-65.
Abstract PS10-14: Efficacy and safety of palbociclib (PAL) in patients (pts) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with preexisting conditions: A post hoc analysis of PALOMA-2
Authors: Gelmon Karen , Walshe Janice M , Mahtani Reshma , Joy Anil A , Karuturi Meghan , Neven Patrick , Lu Dongrui Ray , Kim Sindy , Schnell Patrick , Bananis Eustratios , Schwartzberg Lee
Published: February 2021

Background: In the PALOMA-2 trial, PAL + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in pts with ER+/HER2– ABC. This post hoc analysis assessed efficacy and safety of PAL + LET in pts from PALOMA-2 with baseline preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Methods: Postmenopausal pts with ER+/HER2– ABC received PAL (125 mg/d, 3/1 schedule) + LET (2.5 mg/d, continuous) or PBO + LET. Pts were grouped by the following MedDRA SOC preexisting conditions: Gastrointestinal, Musculoskeletal, Metabolism, and Vascular/Cardiac. Baseline characteristics, PFS, and safety were assessed. Results: At baseline, 41.4% of pts had preexisting gastrointestinal disorders, 58.6% musculoskeletal disorders, 38.9% metabolism disorders, and 57.4% vascular/cardiac disorders. Baseline characteristics were similar between treatment arms within each subgroup and also between subgroups. Within each subgroup, ≥40% of pts also had ≥1 of the other coexisting conditions. Median PFS (mPFS) was significantly longer with PAL + LET vs PBO + LET regardless of preexisting condition (Table). In general, adverse events (AEs) were more frequent with PAL + LET in all subgroups; neutropenia was most common. Within each treatment arm, AEs and dose modifications due to AEs were similar regardless of preexisting condition. Conclusion: PAL + LET showed prolonged PFS and a consistent safety profile regardless of baseline preexisting condition in pts with ER+/HER2– ABC. Clinical trial identification: Pfizer Inc (NCT01740427)

TablePreexisting ConditionPAL + LETPBO + LETPAL + LET vs PBO + LETnmPFS (95% CI)nmPFS (95% CI)HR (95% CI)P ValueGastrointestinal17627.6 (17.5–33.1)10013.6 (11.0–18.5)0.57 (0.42–0.78)<0.001Musculoskeletal25227.6 (21.4–33.1)13816.3 (11.2–19.1)0.53 (0.41–0.69)<0.001Metabolism18627.6 (19.3–30.6)7313.8 (8.3–27.4)0.62 (0.44–0.87)0.003Vascular/Cardiac25430.4 (25.1–36.2)12814.5 (11.0–18.5)0.51 (0.39–0.66)<0.001

Citation Format: Karen Gelmon, Janice M Walshe, Reshma Mahtani, Anil A Joy, Meghan Karuturi, Patrick Neven, Dongrui Ray Lu, Sindy Kim, Patrick Schnell, Eustratios Bananis, Lee Schwartzberg. Efficacy and safety of palbociclib (PAL) in patients (pts) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with preexisting conditions: A post hoc analysis of PALOMA-2 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-14.
Abstract PS10-30: An open label, pilot study of veliparib and lapatinib in patients with metastatic, triple negative breast cancer
Authors: Stringer-Reasor Erica M , May Jori E , Olariu Eva , Caterinicchia Valeria , Li Yufeng , Manna Deborah Della , Rocque Gabrielle B , Vaklavas Christos , Falkson Carla I , Nabell Lisle M , Acosta Edward P , Forero-Torres Andres , Yang Eddy S
Published: February 2021

Purpose: Poly (ADP-ribose)-polymerase inhibitors (PARPi) have been approved for cancer patients with germline BRCA1/2(gBRCA1/2) mutations, and efforts to expand the utility of PARPi beyond BRCA1/2 are ongoing. In preclinical models of triple negative breast cancer (TNBC) with intact DNA repair, we previously showed an induced synthetic lethality with combined EGFR inhibition and PARPi. We report the safety and clinical activity of lapatinib and veliparib in patients with metastatic TNBC. Experimental Design: A first-in-human, pilot study of lapatinib and veliparib was conducted in metastatic TNBC (NCT02158507). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rates and pharmacokinetic evaluation. Gene expression analysis of pre-treatment tumor biopsies was performed. Key eligibility included TNBC patients with measurable disease and prior anthracycline and taxane therapy. Patients with gBRCA1/2 mutations were excluded. Results: Twenty patients were enrolled of which 17 were evaluable for response. Median number of prior therapies in the metastatic setting was 1 (range 0-2). Fifty percent of patients were Caucasian, 45% African-American, and 5% Hispanic. Of evaluable patients, 4 demonstrated a partial response and 2 had stable disease. There were no dose-limiting toxicities. Most AEs were limited to grade 1 or 2 and no drug-drug interactions noted. Gene expression analysis suggest baseline DNA repair pathway score was lower and baseline immunogenicity was higher in the responders compared to non-responders. Conclusions: Lapatinib plus veliparib therapy has a manageable safety profile and promising antitumor activity in advanced TNBC. Further investigation of dual therapy with EGFR inhibition and PARP inhibition is needed.

Citation Format: Erica M Stringer-Reasor, Jori E May, Eva Olariu, Valeria Caterinicchia, Yufeng Li, Deborah Della Manna, Gabrielle B Rocque, Christos Vaklavas, Carla I Falkson, Lisle M Nabell, Edward P Acosta, Andres Forero-Torres, Eddy S Yang. An open label, pilot study of veliparib and lapatinib in patients with metastatic, triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-30.
Abstract PS11-01: Outcome without adjuvant systemic treatment in breast cancer patients included in the MINDACT trial
Authors: Cardozo Josephine MN Lopes , Byng Danalyn , Drukker Caroline A , Schmidt Marjanka K , van 't Veer Laura J , Cardoso Fatima , Piccart Martine , Poncet Coralie , Rutgers Emiel JTh
Published: February 2021

Background: Adjuvant systemic treatments have played an important role in the decline of breast cancer mortality over the years. Because of the extensive short- and long-term toxicities associated with these treatments, careful selection of patients likely to benefit from them is needed. Studies have shown excellent survival in subgroups of patients receiving no adjuvant systemic treatments. Some national guidelines advise no adjuvant systemic treatments in specific groups of patients with clinical low risk breast cancer. The aim of this study is to investigate the survival of breast cancer patients who received no adjuvant treatment (chemotherapy nor endocrine therapy) using data from the EORTC 10041/BIG 3-04 MINDACT trial. Material and methods: Of the 6693 patients enrolled in the MINDACT trial, accrued 2007-2011, 509 patients with hormone receptor positive, HER2 negative, lymph node negative tumors <2cm received no adjuvant systemic treatment, mostly following local recommendations. Median follow-up was 8.7 years. Using propensity score matching and exact matching, we will identify groups of patients treated with adjuvant endocrine therapy and/or chemotherapy with similar tumor characteristics to the untreated patients. We will use the Kaplan-Meier method to estimate distant metastasis free interval and overall survival at 5 and 8 years for each group. Differences between groups will be evaluated using the log-rank test, and hazard ratios with 95% CI derived from Cox proportional hazards models. Planned analyses: The long-term data of the MINDACT trial has recently become available. The date of planned analysis is August 10th 2020.For this study, the primary clinical endpoint will be distant metastasis free interval, which will be assessed in the matched groups of untreated patients, patients who received endocrine therapy only, and patients who received chemotherapy with or without endocrine therapy. Kaplan-Meier estimates will be provided at 5 years, and at 8 years to assess the long-term outcomes in this population. A statistical plan for this analysis was specifically developed and approved prior to performing any analysis.

Citation Format: Josephine MN Lopes Cardozo, Danalyn Byng, Caroline A Drukker, Marjanka K Schmidt, Laura J van 't Veer, Fatima Cardoso, Martine Piccart, Coralie Poncet, Emiel JTh Rutgers. Outcome without adjuvant systemic treatment in breast cancer patients included in the MINDACT trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-01.
Abstract PS12-11: Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer
Authors: Hu Xichun , Cao Jun , Wang Biyun , Zhang Jian , Wang Leiping , Tao Zhonghua , Li Ting
Published: February 2021

Background HX008 is a humanized IgG4S228P anti-PD-1 monoclonal antibody with an engineered Fc domain. Gemcitabine plus cisplatin (GP) has shown satisfying antitumor activity as first-line therapy for metastatic triple-negative breast cancer (mTNBC) in CBCSG 006 trial (ClinicalTrials.gov, NCT01287624). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of HX008, combined with GP in patients with mTNBC in first-line setting. Methods Eligible patients are mTNBC with ≥6 months DFI who never receive antitumor therapy for metastatic disease. Participants received HX008 at 3mg/kg (d1, q3w) plus gemcitabine at 1250mg/m2 (d1, 8, q3w) and cisplatin 75mg/m2 (d1, q3w). At most 6 cycles of GP chemotherapy were given, while HX 008 could be maintained until disease progression or unacceptable toxicity occurred. Results Between July 2019 and March 2020, a total of 31 patients were enrolled in this study. Median (range) age was 50 (29-69) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other 6 (19.4%) experienced stable disease (SD). The median progression free survival (PFS) was 9.07 months (95%CI,7.29m-13.01m). The PFS data was not yet mature, for nearly half of the intent-to-treat population has not progressed by October 9, 2020. The most common treatment-related adverse events of grade 3 or 4 included neutropenia (71.0%), anemia (55.5%), thrombocytopenia (32.3%), hypocalcemia (9.68%), hypokalemia (6.45%), and Alanine aminotransferase increased (6.45%). There were no treatment-related deaths. Conclusion HX008 plus GP demonstrated promising activity and manageable safety in patients with mTNBC in first-line setting. Clinical trial information: CHINADRUGTRIALS.ORG, CTR 20191353.

Citation Format: Xichun Hu, Jun Cao, Biyun Wang, Jian Zhang, Leiping Wang, Zhonghua Tao, Ting Li. Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-11.
Abstract PS13-37: Effectiveness of eribulin in poor prognosis subgroups of metastatic breast cancer (mBC) patients (elderly, African Americans, and patients with liver metastases) in the United States
Authors: Mougalian Sarah S. , Kish Jonathan K. , Zhang Jingchuan , Liassou Djibril , Feinberg Bruce A.
Published: February 2021

Background: Eribulin mesylate was approved in the United States (US) in 2010 as third-line or later treatment (after an anthracycline and a taxane) of mBC. Multiple patient demographic and clinical characteristics have been reported to impact clinical outcomes in mBC patients. The objective of these analyses was to assess real-world clinical outcomes of eribulin therapy in three subgroups that generally have poorer prognoses: elderly (≥65 years), African American, and those with liver metastases in clinical practice in the US. Methods: A retrospective chart review study was conducted across community oncology practices in the US. Adult female patients with mBC who initiated treatment with eribulin as per US prescribing information between 2011 and 2017 were included. Data were extracted by prescribing physicians from individual patient’s electronic health records and captured via an electronic case report form. All patient data were de-identified prior to analyses. Clinical outcomes including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed in patients who were elderly, African American, or who had liver metastases. Results: Current analyses were based on data from 278 patients including 175 (63%) patients with liver metastases, 98 (35%) elderly patients, and 73 (26%) African American patients. Mean age at initiation of eribulin in each group was: liver metastases, 59; elderly, 71; and African American, 58. Proportion of patients with ECOG-PS ≥2 at initiation of eribulin was: liver metastases, 46%; elderly, 52%; and African American, 47%. The majority of patients received eribulin in 3rd line: liver metastases, 80%; elderly, 87%; and African American, 85%. ORR to eribulin was 34% in patients with liver metastases, 35% in elderly, and 48% in African Americans. Median PFS from initiation of eribulin was 5.2 months in patients with liver metastases, 5.8 months in elderly, and 7.6 months in African Americans. Landmark OS from initiation of eribulin at 6, 12 and 24 months were 71%, 36% and 18%, respectively, in patients with liver metastases, 72%, 35% and 23% in elderly, and 78%, 46%, and 28% in African Americans. Conclusion: Effectiveness of eribulin in clinical practice in patients with liver metastases, elderly, and African Americans was confirmed within this real-world study in the US.

Citation Format: Sarah S. Mougalian, Jonathan K. Kish, Jingchuan Zhang, Djibril Liassou, Bruce A. Feinberg. Effectiveness of eribulin in poor prognosis subgroups of metastatic breast cancer (mBC) patients (elderly, African Americans, and patients with liver metastases) in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-37.
Abstract PS14-17: Rapamycin inhibits stem cell function and diminishes inflammation and senescence markers in human mammary gland
Authors: Bouamar Hakim , Broome Larry , Gu Xiang , Nazarullah Alia , Brenner Andrew , Kaklamani Virginia , Jatoi Ismail , Sun Lu-Zhe
Published: February 2021

Gene expression profiles of some subtypes of breast cancer were shown to correspond to the profiles of the basal or luminal mammary stem/progenitor cell-enriched epithelial cells implicating the mammary stem cells (MaSCs) as tumor-initiating cells for certain types of breast cancer. Moreover, there is growing evidence that MaSCs may initiate neoplastic transformation when dysregulated in mouse models. We have previously reported an increased frequency of the MaSC-enriched Lin-/CD49fhigh/CD24+ basal cells in old mice (>27 month) compared to young ones (2-4 month) along with an increase of hyperplasic lesions. Gene expression profile revealed an increase of immune and inflammatory responses in old basal cells and stroma cells indicating that aging-induced immune and inflammatory responses might initiate basal cell expansion and transformation. Our preliminary data on mice using rapamycin, an immune and inflammation inhibitor, were very encouraging so we decided to start a clinical window trial (NCT02642094) to test whether rapamycin could reduce biomarkers associated with progression to invasive breast cancer and MaSC numbers in postmenopausal patients with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS). The patients enrolled in the trial took rapamycin (sirolimus, 2mg/day) for 5-7 days with 3-7 days of washout before surgery. The adjacent non-tumor surgical tissues were used for the measurements of sphere formation efficiency (SFE) of the basal and luminal cells. The control group were patients with ADH/DCIS who did not take the drug. Rapamycin treatment significantly diminished the SFE of the basal MaSC. Immunohistochemical staining of the biopsies and surgical tissues showed that rapamycin treatment significantly decreased the levels of COX2 (an inflammation marker) and p16 (a senescence marker), and moderately increased p62 (an autophagy marker). Furthermore, rapamycin significantly reduced the proliferation marker Ki67 staining. In conclusion, rapamycin inhibits MaSCs function and senescence and inflammation features in human mammary glands. Whether the suppression of the senescence-associated inflammatory responses is the mechanism by which rapamycin suppresses MaSC function is under investigation.

Citation Format: Hakim Bouamar, Larry Broome, Xiang Gu, Alia Nazarullah, Andrew Brenner, Virginia Kaklamani, Ismail Jatoi, Lu-Zhe Sun. Rapamycin inhibits stem cell function and diminishes inflammation and senescence markers in human mammary gland [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-17.
Abstract PS14-25: Outcomes of metastatic male breast cancer
Authors: Dogan Izzet , Khanmammadov Nijat , Aydıner Adnan , Saip Pınar
Published: February 2021

Background: Breast cancer is rare in men. The prognosis of male breast cancer (MBC) is poor than female breast cancer. The study aims to evaluate the clinical features and prognosis in metastatic male breast cancer (mMBC).

Method: The data of 28 patients were retrospectively reviewed. The clinical and histopathological features of the patients were recorded. Overall survival (OS) and prognostic factors evaluated with Kaplan-Meier analysis and Cox-regression analysis.

Results: The median follow-up period was 55.1 months (range, 6.6-205.6). The median age at diagnosis was 57 years (range, 26-86). Seven (27%) of the patients were de-novo metastatic. Invasive ductal carcinoma (92.6%) was the most common pathological subtype. The ratio of HER2 positivity in patients was 21.6%, and estrogen and progesterone receptor's positivity were 96.4% and 71.4%, respectively. The most common metastatic locations of disease were bone-75%, lung-39.3%, brain-21.4%, and surrenal-10.7%. Six of the patients received trastuzumab-based chemotherapy. A total of 14 (50%) patients deceased during the study period. The median OS was 42.6±10.7 months (range, 21.6-63.7) for all patients. One-, three- and five-years overall survival ratios were 95.7%, 54.2%, and 36.6%, respectively. In univariate analysis, Brain metastasis (p=0.033), the number of metastatic sites (p=0.045), and the history of regular alcohol consumption (p=0.008) were a statistically significant factor on OS. However, the results were not confirmed in multivariate analysis. Also, we found that trastuzumab-based treatment and de-novo metastasis were not affecting on OS in mMBC.

Conclusions: Due to the rarity, the data of mMBC is limited. In this study, we observed that the prognosis of mMBC was poor. Despite the low number of patients, we detected that having brain metastasis, the number of metastatic sites, and history of alcohol consumption may be a prognostic factor in univariate analysis.

Citation Format: Izzet Dogan, Nijat Khanmammadov, Adnan Aydıner, Pınar Saip. Outcomes of metastatic male breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-25.
Abstract PS14-26: Comparison of clinicopathological features in BRCA-wild type and -mutated male breast cancer patients
Authors: Dogan Izzet , Aydın Esra , Yazıcı Hülya , Saip Pınar
Published: February 2021

Background: BRCA mutations result in a variety of cancer types such as breast, ovarian, and prostate. 4-40% of the patients with male breast cancer have BRCA mutations, and BRCA 2 mutation is more commonly detected. In this study, we compared the clinicopathological characteristics of BRCA- wild type and -mutated male breast cancer (MBC).

Methods: The data of 43 patients were retrospectively reviewed. Clinical and histopathological data of the patients were recorded. The characteristics of the patients were compared by the chi-square test and Fisher exact test. Survival analysis evaluated with Kaplan-Meier analysis.

Results: The median follow-up period was 35.8 months (range, 2.2-225.8). The median age at diagnosis was 58 years (range, 25-81) and not statistically different between groups (p=0.753). 11 (25.6%) of the patients had BRCA mutations. Four (9.3%) patients had BRCA1 mutations, six (14%) patients BRCA2 mutations, and one (2.3%) patients had both BRCA 1 and 2 mutations. Among BRCA- wild type and - mutated patients: estrogen receptor positivity (p=0.055), progesterone receptor positivity (p=0.698), HER2 overexpression (p=0.542), tumor localization (p=0.305), tumor histology (p=0.069), lymph node involvement (p=0.589), tumor stage (p=0.892), and recurrence status (p=0.698) were comparable. The median overall survival was 115.6 months (range, 76.0-155.3), and similar between groups (p=0.647).

Conclusions: MBC is rare. In literature, the data of MBC and BRCA mutation is limited, and studies included a low number of patients. In a result, we found that clinicopathological characteristic and prognosis of BRCA-mutated and-wild type MBC was similar.

Citation Format: Izzet Dogan, Esra Aydın, Hülya Yazıcı, Pınar Saip. Comparison of clinicopathological features in BRCA-wild type and -mutated male breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-26.
Abstract PS14-28: Core−shell structured gold nanorods@iron-based metal-organic framework for magnetic resonance imaging guided photothermal therapy in triple-negative breast cancer
Authors: He Jingchao , Zhang Haijun
Published: February 2021

Background/Objective: As the most aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) with high mortality lacks effective treatment options and results in poor prognosis. Photothermal therapy (PTT) has emerged as a potential anticancer strategy. Until now, the construction of multifunctional photothermal agents is vital importance for effective PTT generally. In this work, the novel core-shell gold nanorods (GNs)@iron-based metal-organic framework (Fe-MOF) was firstly successfully fabricated for magnetic resonance imaging (MRI) guided PTT in TNBC. The inner GNs have excellent photothermal properties and the outer Fe-MOF shell endow the nanocomposite with superior T2 MRI property.Methods: The GNs @ Fe-MOF was firstly prepared by a layer-by-layer technique. Prepared nanocomposite was characterized by measuring measuring measuring transmission electron microscope (TEM), UV-Vis-NIR absorption spectra, powder X-radiffraction (XRD) patterns. MR imaging of nanocomposite was assessed in vitro and in vivo. The biocompatibility and photothermal cytotoxicity of the nanocomposite was assessed by a CCK-8 assay. The photothermal effect of nanocomposite in vivo was evaluated by monitoring tumor growth. The tumor tissues were analyzed by Hema-toxylin and eosin (H&E) to further analyze photothermal effect. The toxicity of the materials in major organs was also investigated by H&E.Result: The core-shell GNs @ Fe-MOF was successfully prepared and displayed excellent dispersion. The nanocomposite possessed good biocompatibility and effectively killed tumor cells under laser irradiation. Meanwhile, the nanocomposite showed clear signal contrast in T2-weighted images in vitro and in vivo. Moreover, the nanocomposite significantly inhibited tumor growth under laser irradiation in vivo. H&E showed that the nanocomposite caused serious damage to tumor tissue under laser irradiation.Conclusion: The current work developed a novel multifunctional core-shell GNs @ Fe-MOF with good biocompatibility for MRI guided PTT in TNBC.Keywords : Magnetic resonance imaging, Photothermal therapy,gold nanorods@iron-based metal-organic Framework

Citation Format: Jingchao He, Haijun Zhang. Core−shell structured gold nanorods@iron-based metal-organic framework for magnetic resonance imaging guided photothermal therapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-28.
Abstract PS16-11: Potential therapeutic effects of HDACi FK228 on TNBC using various models
Authors: Alzoubi Madlin , Nguyen Khoa , Hebert Katherine , Matossian Margarite , Burks Hope , Collins-Burow Bridgette , Burow Matthew
Published: February 2021

Breast cancer is the most prevalent type of cancer among women. Most breast cancers are hormone sensitive, however triple negative breast cancer (TNBC), a more aggressive subtype of breast cancer is characterized by its negative expression of estrogen and progesterone receptors, and lack of Her2/NEU amplification. Because of its receptor status, hormone receptor targeted treatments are ineffective against TNBC making it difficult to treat. FK228, known as Romidepsin, is a histone deacetylase inhibitor (HDACi) that specifically targets the enzymes HDACs 1 and 2, tumor suppressor and other proteins exerting epigenetic changes on tumor cells resulting in anticancer activity. FK228 has not been studied in TNBC, but has been approved by the FDA for the treatment of peripheral T-cell lymphoma (PTCL), where the mechanism of action has demonstrated cell cycle arrest and apoptosis [1,2]. To assess the preliminary role of FK228 in breast cancer, a number of TNBC cell lines were treated with the drug and analyzed for suppression of cell cycle genes. Similar to PTCL, TNBC cell lines showed an increase in cell cycle arrest genes such as p21 and others subsequent to treatment. Moving forward, to recapitulate the tumor microenvironment we have utilized 2D and 3D culture, while PDXs (patient derived xenografts), an excellent translational tool. We first identified changes in morphology and migration in 2k1, MDA-MB 231 and HS-578t cell lines treated with FK228 under in-vitro conditions. Additional molecular studies also show a reversal of the epithelial to mesenchymal transition (EMT) in FK228 treated BC cell lines; specifically in relation to EMT genes CDH1 and ZEB2, both directly connected to HDAC1/2 activity. To further study the effects of FK228, PDXs are implanted into mice to study growth patterns, recurrence, metastatic potential and response to FK228 in different patient tumor models. FK228 showed a drastic suppression in tumorigenesis in model TU-BCX-2O0, prompting the study of several other models in tumorigenesis including TU-BX-4IC, 4M4 and 4QX. Metastasis was also monitored by H&E staining lung and liver tissue for analysis for each model, and using an in vivo model consisting of GFP/luciferase transfected breast cancer cells MDA-MB-231 and SUM-159 to monitor both the proliferation and spread of disease in mice. Ultimately this study aims to characterize the FK228 alteration of pathways involved in tumorigenesis, metastasis and resistance within TNBC.

Citation Format: Madlin Alzoubi, Khoa Nguyen, Katherine Hebert, Margarite Matossian, Hope Burks, Bridgette Collins-Burow, Matthew Burow. Potential therapeutic effects of HDACi FK228 on TNBC using various models [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-11.