bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PS7-13: Associations between frailty and cancer-specific mortality among older women with breast cancer
Authors: Yan Connie H , Coleman Chandler , Nabulsi Nadia A , Chiu Brian , Ko Naomi Y , Hoskins Kent , Calip Gregory S
Published: February 2021

PURPOSE Frailty is assessed when making treatment decisions among older women with breast cancer (BC), which in turn impacts survival. We evaluated associations between frailty and risks of BC-specific and all-cause mortality in older women.

METHODS We conducted a retrospective cohort study of Medicare beneficiaries ages ≥65 years with stage I-III BC using the Surveillance, Epidemiology and End Results Medicare Health Outcome Survey Data Resource. Frailty was measured using the deficit-accumulation frailty index, categorized as robust, pre-frail or frail, at baseline and during follow-up. Fine and Gray competing risk and Cox proportional hazards models were used to estimate sub-distribution hazard ratios (SHR) and hazard ratios (HR) with 95% confidence intervals (CI) for BC-specific and all-cause mortality, respectively.

RESULTS Among 2,411 women with a median age of 75 years at BC diagnosis, 50% were categorized as robust, 29% were pre-frail and 21% were frail. Compared to robust women, fewer frail women received breast-conserving surgery (52% vs. 63%) and radiation (44% vs. 52%). In multivariable analyses, frail women had higher risks of all-cause mortality compared to robust women (HR 2.16, 95% CI 1.80-2.60).

CONCLUSION Frail women in our study had a higher cumulative hazard of BC-specific death, but this observed higher risk was not significant after accounting for differences in treatment and competing risks of other-cause death. Measuring frailty may help determine overall life expectancy but not BC-specific death.

Table. Risk of Breast Cancer-Specific and All-cause Mortality, using time-varying DAFI measureEventsCrude SHRRobust 95%CIP-valueMinimally Adjusted SHRaRobust 95%CIP-valueFully Adjusted SHRbRobust 95%CIP-valueBreast Cancer-Specific MortalityDAFI CategoriesRobust891.001.001.00Pre-frail691.250.91 – 1.700.161.150.84 – 1.590.381.060.77 – 1.480.72Frail621.531.11 – 2.110.011.371.00 – 1.900.051.190.85 – 1.660.31All-Cause MortalityDAFI CategoriesRobust2721.001.001.00Pre-frail2241.551.30 – 1.84<0.00011.411.19 – 1.68<0.00011.371.15 – 1.63<0.0001Frail2362.32.12 – 3.02<0.00012.331.96 – 2.78<0.00012.161.80 – 2.60<0.0001DAFI = deficit-accumulation frailty index; HR = hazard ratio; SHR = subdistribution hazard ratios; CI = confidence intervalsa adjusted for age categories and breast cancer staging b adjusted for age categories, breast cancer staging, surgery type, radiation, Estrogen/Progestin Receptor, race/ethnicity, marital status, and education

Citation Format: Connie H Yan, Chandler Coleman, Nadia A Nabulsi, Brian Chiu, Naomi Y Ko, Kent Hoskins, Gregory S Calip. Associations between frailty and cancer-specific mortality among older women with 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 PS7-13.
Abstract PS7-64: Breast cancer in young women in a tertiary-level hospital in Guatemala
Authors: Alvarado-Muñoz Juan F , Reyes-Morales Agatha , Kihn-Alarcón Alba J , Chivalan Marco , Torselli Silvana , Puac-Polanco Victor
Published: February 2021

Background: Breast cancer is the frequent neoplasia in young women, which in developing countries is associated with more adverse outcomes. In Latin America, reports have shown an increased incidence of breast cancer in young women. No information exist regarding breast cancer characteristics in young Guatemalan women. We aimed to describe the clinical-pathological features among women aged 45 years or less treated in a tertiary-level hospital in Guatemala. Methods: We examined data from 119 women aged 45 years or less diagnosed with primary invasive breast cancer at the Oncology Unit Roosevelt Hospital in Guatemala between 2016 and 2020. Data were drawn from medical files on sociodemographic characteristics, histology, clinical stage, and breast cancer subtypes.Results: Of the total sample, breast cancer in women aged 45 years or less represented 31.2% of the cases. Of these, 24.36% is before 35 years, 28.57% between 35 to 39 years, and 47.05% between 39 to 45 years. Advanced clinical stages affected 66.6% of young women (48.33% for stages III and 18.33% stage IV). Data from specific breast cancer molecular subtype showed that 72.35% of cases in young women expressed an aggressive molecular subtype (Her-2 positive 27.06%, triple-negative 21.76%, and luminal/Her-2 positive 23.53%). Regarding treatment, most young patients received surgical treatment, as well as neoadjuvant or adjuvant chemotherapy. Only 24.37% received hormonal and 26.89% radiation therapy. Conclusions: Our finding suggested that young women treated for breast cancer at a tertiary-level hospital in Guatemala had a high proportion of aggressive molecular subtypes and a high rate of locally advanced disease. This aggressive cancer behavior among young women is consistent with findings in other Latin American countries. Evidence examining risk factors for aggressive cancer in young women, such as delay in diagnosis and treatment timing, is warranted.

Table 1. Distributions of socio-demographic and cancer-related characteristics variables% (SE)n = 119ETHNIC GROUPMayan Indigenous12.61 (3.05)No-Mayan Indigenous87.39 (3.05)HISTOLOGYDuctal96.64 (1.66)Lobular1.68 (1.18)Other1.68 (1.18)CLINICAL STAGE*I1.67 (1.17)II31.67 (4.26)III48.33 (4.58)IV18.33 (3.54)BREAST CANCER SUBTYPELuminal27.65 (4.76)Her2 positive27.06 (5.11)Triple-negative21.76 (5.05)Luminal/Her223.53 (6.61)TREATMENTSurgery55.46 (4.58)Neoadjuvant Chemotherapy82.35 (3.51)Adjuvant Chemotherapy47.06 (4.59)Radiotherapy26.89 (4.08)Hormonotherapy24.37 (3.95)

Citation Format: Juan F Alvarado-Muñoz, Agatha Reyes-Morales, Alba J Kihn-Alarcón, Marco Chivalan, Silvana Torselli, Victor Puac-Polanco. Breast cancer in young women in a tertiary-level hospital in Guatemala [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 PS7-64.
Abstract PS7-84: Lymphovascular invasion among female patients diagnosed with breast cancer
Authors: Singh Maharaj , Konduri Santhi , Rovin Richard
Published: February 2021

Background The presence of carcinoma cells in either lymphatic vessels, blood vessels or both is defined as lymphovascular invasion (LVI). The presence of LVI is associated with an increased risk of axillary lymph node and distant metastases. LVI is also characterized as one of the significant prognostic factors for the patients diagnosed with breast cancer. Objective The objective of this study is to identify predictors of LVI among female patients diagnosed with breast cancer. Method From the Commission on Cancer’s National Cancer Database from 2010 through 2016, we identified 1,220,046 female patients diagnosed with breast cancer and with non-missing value for LVI. Patient demographics, tumor characteristics and biomarkers were analyzed using descriptive statistics. Odds ratios (OR) were computed using stepwise multivariate logistics regression. All statistical analysis was done using SAS version 9.4, SAS institute, Cary, NC and for all statistical tests alpha of 0.05 was used. Results The study population included 78% non-Hispanic white (NHW), 11% non-Hispanic black, (NHB), 5% Hispanic and 6% from ‘other’ race category. The median age of the patients at the time of diagnosis was 61 years. Of the total patients, only 16 % had LVI. Significant predictors of LVI include race (Hispanic vs NHW, OR=1.03, 1.01-1.06 p=0.008; NHB vs NHW OR=0.91,0.90-0.93, p<0.001; ‘Other’ vs NHW OR=0.97, 0.95-1.00, p=0.018), insurance status (government vs no-insurance, OR=1.08,1.04-1.11, p<0.001; private vs no-insurance, OR=1.08,1.05-1.12, p<0.001), Charlson-Dayo Index (1 vs none, OR=1.08, 1.06 -1.09, p<0.001, 2 vs none, OR=1.16, 1.12 -1.20, p<0.001, 3 or more vs none, OR=1.16, 1.10 -1.22, p<0.001), primary sequence (OR=1.03,1.01-1.04, p<001), cancer stage (I vs 0, OR=2.99, 2.86-3.14, p <0.0001, II vs 0, OR=9.40,8.97-9.86 p <0.0001, III vs 0, OR=21.28, 20.25-22.36, p <0.0001, and IV vs 0, OR=15.11,14.32-15.94, p <0.001), ER (OR=1.02, 1.01-1.04 p=0.002), PR (OR=1.03, 1.01-1.05 p=0.002), HER2neu (equivocal vs negative OR=1.14, 1.10-1.18 p <0.001, positive vs negative OR=1.28, 1.26 -1.30, p <0.001), and 10 year increment in age at the time of diagnosis (OR=0.90, 0.89-0.90, p <0.001). Conclusion The predictive factors for LVI includes Hispanic race, government or private insurance, higher Charlson-Dayo scores, primary sequence, cancer stages, ER, PR and HER2neu expression. The chances LVI decreases with increasing age. These finding might provide insights for clinicians for the treatment plan for the patients.

Citation Format: Maharaj Singh, Santhi Konduri, Richard Rovin. Lymphovascular invasion among female patients diagnosed with 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 PS7-84.
Abstract PS7-87: Incidence, treatment and survival of patients with brain metastases at initial metastatic breast cancer diagnosis: A real-world experience in national cancer center, China
Authors: Li Yiqun , Li Qiao , Mo Hongnan , Guan Xiuwen , Lin Shaoyan , Wang Zijing , Chen Yimeng , Zhang Ye , Zhang Dainan , Chen Shanshan , Cai Ruigang , Wang Jiayu , Luo Yang , Fan Ying , Yuan Peng , Zhang Pin , Li Qing , Ma Fei , Xu Binghe
Published: February 2021

Background: To characterize the incidence, treatment and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. Methods: The China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 to 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. Results: Brain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40 -4.04; p <0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02-3.51; p =0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52-6.87; p =0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p=0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment. Conclusion: HER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive or triple-negative diseases or with extensive extracranial metastases. First-line TKI and multidisciplinary treatment helped to extend survival.

Citation Format: Yiqun Li, Qiao Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Zijing Wang, Yimeng Chen, Ye Zhang, Dainan Zhang, Shanshan Chen, Ruigang Cai, Jiayu Wang, Yang Luo, Ying Fan, Peng Yuan, Pin Zhang, Qing Li, Fei Ma, Binghe Xu. Incidence, treatment and survival of patients with brain metastases at initial metastatic breast cancer diagnosis: A real-world experience in national cancer center, China [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 PS7-87.
Abstract PS8-21: The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC)
Authors: Yariv Orly , Yerushalmi Rinat , Moore Assaf , Shohat Tzippy , Rotem Ofer , Ceder Yasmin Korzets , Goldvaser Hadar
Published: February 2021

Background: Oral contraceptives (OC) and hormone replacement therapy (HRT) are well-established risk factors for ER positive breast cancer. Infertility is associated with an increased breast cancer risk and there is conflicting data on the influence of fertility treatments on breast cancer risk. The impact of exogenous estrogen exposure on breast cancer characteristics is not well described. Methods: A single center retrospective cohort study comprising all women with ER positive, human epidermal growth factor receptor 2 (HER2) negative, EBC whose tumors were sent to OncotypeDX analysis and were treated in our institute between 2005 and 2012. Data on exogenous estrogen exposure were collected including: OC and HRT use and prior fertility treatments. The impact of these exposures was assessed on pre-specified histopathological features including: tumor size, nodal status, ER and progesterone receptor (PR) staining, grade, Oncotype recurrence score (RS), ki67, lymphovascular and perineural invasion.

Results: A total of 620 women were included, 79% (Num) were postmenopausal. Prior exposure to OC, HRT and fertility treatments was documented in 19% (103), 30% (136) and 11% (62), respectively. OC use was associated with smaller (≤1cm) tumors (30% vs. 20%, p=0.023) and were less likely to have grade 3 disease (10% vs. 19%, p=0.049). No other associations were found between exogenous estrogen exposures and tumor characteristics (Table).

Conclusions: Use of OC may be associated with breast cancer with a distinct features compared to women with luminal breast cancer without history of OC use. Large scale studies are needed to better characterize these findings.

Fertility treatmentHRT ≥ 2 yearsHRTOCPNo (%)Yes(%)PNo(%)Yes (%)PNo (%)Yes (%)PNo(%)Yes(%)0.1722254252165150.7002355222057240.7002255232456200.023205723304426T≤1 cm 12 cm0.85917180.09815200.09815210.6671815Node positive0.06479138891100.29982126761590.29982135771590.207791488795IDC ILC Other0.1671864181473130.5001667181664190.5001667171762210.049186319187310Grade 1 230.18922078329680.70811781122770.70811781221780.7392227732275ER intensity≤1 120.1121470.67116150.67116140.103148PR Negative1.000530.455520.455530.28252PNI present0.772670.351780.351570.056105LVI present0.18620290.36222190.36223180.5282218Ki67 >20%0.85917180.78718160.78717180.5701816Oncotype RS>25

Citation Format: Orly Yariv, Rinat Yerushalmi, Assaf Moore, Tzippy Shohat, Ofer Rotem, Yasmin Korzets Ceder, Hadar Goldvaser. The impact of exogenous estrogen exposure on the characteristics of estrogen receptor (ER) positive, early-stage breast cancer (EBC) [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 PS8-21.
Abstract PS8-24: Clinical and pathologic characteristics of Turkish breast cancer (BC) patients screened with BRCA1, BRCA2 or 26 - gene inherited cancer panel testing: Single institution experience
Authors: Isiklar Aysun , Soyder Aykut , Yararbas Kanay , Ekmekci Cumhur , Yazici Hulya , Basaran Gul
Published: February 2021

Background: BRCA1 and BRCA2 mutations are responsible for two thirds of hereditary BC. Germline genetic testing for BC susceptibility has evolved from a single-gene analysis to a multigene panel testing. Identification of a pathogenic mutation in BRCA and other panel represent a therapeutic opportunity today. Methods: We aimed to investigate clinical and pathologic characteristics of BC patients who were referred to our center between 2011-2019 and underwent BRCA1, BRCA2 or 26-gene inherited cancer panel testing based on NCCN criteria for hereditary breast/ovarian cancer testing. We analyzed the frequency of pathogenic mutations and its relationship with clinical and pathologic factors. Results: A total of 576 patients were identified. Among them 356 (63%) had their test in our university, 218 (38%) patients had their test at other centers. Sixty-six % (n:376) of patients had panel testing, 34% had only BRCA 1-2 mutation test. Median age was 42(22-87) and 5 patients were male. Ten % of patients had metastatic disease, 70% had early BC and 20% had locally advanced stage at the time of referral. The indication for genetic testing was family history in 169 (29%) patients, triple negative (TN) subtype in 100 (17%) patients and age <45 years in 260 (45%) patients. Seventy-nine % of patients were premenopausal. A total of 114 (19%) patients had pathogenic mutations. The most commonly mutated genes were BRCA1 (n:38, 6%), BRCA2 (n:35, 6%), ATM (n:6), p53 (n:5), PALB2 (n:5), CHEK2 (n:5). Six patients had more than one pathogenic mutation. Among patients with pathogenic mutations 58% had ER positive, 27% had TN and 15 % had Her-2 positive disease. Thirty-four % of patients with TN tumors have pathogenic mutations, 23% of patients with TN tumors had BRCA mutations. TP53, PALB2 and CHEK2 mutations were more frequent in HR positive disease. Age <35 (p:0.002), triple negative subtype (p: 0.005) and menopausal status (p:0.001) were significantly associated with having pathogenic mutations in multivariate analysis. Conclusion: Two thirds of BC patients <35 years-old and one third of patients with TN tumors have pathogenic germline mutations in BC predisposing genes when they were screened in line with NCCN criteria.

Citation Format: Aysun Isiklar, Aykut Soyder, Kanay Yararbas, Cumhur Ekmekci, Hulya Yazici, Gul Basaran. Clinical and pathologic characteristics of Turkish breast cancer (BC) patients screened with BRCA1, BRCA2 or 26 - gene inherited cancer panel testing: Single institution experience [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 PS8-24.
Abstract PS8-34: High rates of BRCA1 and BRCA2 germline mutations among Arab patients with triple-negative breast cancer
Authors: Abdel-Razeq Hikmat , Abujamous Lama , Bater Rayan
Published: February 2021

Background: Patients with triple-negative (TN) disease, which represent 10-15% of all breast cancer cases, is associated with the worst prognosis among all breast cancer subtypes. Because of higher risk for BRCA mutation, patients diagnosed at age ≤60 years with triple-negative disease should undergo genetic testing. Identification of BRCA1 or BRCA2 mutation has clinical impact on breast and ovarian cancer prevention and treatment. Many drugs were recently approved for patients with BRCA mutation carriers. We here investigate the patterns and prevalence of BRCA1 and BRCA2 mutations among Arab patients diagnosed with this breast cancer subtypes and treated at our institution. Patients and Methods: We utilized our database of all breast cancer patients, from Jordan and neighboring Arab countries, tested for BRCA mutations (n=1302) as per the NCCN guidelines. Patients with no expression of estrogen (ER) or progesterone (PR) receptors and negative for HER2 (triple-negative) were enrolled regardless of their age or family history. Following a detailed genetic counselling in a clinic established for this purpose, BRCA testing was then performed at 3 reference labs in UK and USA. BRCA1 and BRCA2 mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Results: During the three-year study period, a total of 171 (13.1%) of all patients in database fulfilled our inclusion criteria. Twenty-two (12.9%) patients were from Palestine, Syria and Iraq. Median age was 41 (range, 19-77) years and all were females. Among this group, a total of 45 (26.3%) were tested positive for BRCA1 (n=32, 18.7%) or BRCA2 (n=13, 7.6%) while 12 (7.0%) others had VUS. Mutations were detected in 26 (31.7%) of 82 patients who were triple-negative and diagnosed at age 40 years or younger. Additionally, 26 (36.6%) of 71 patients with triple-negative disease who had one or more close relatives with breast, pancreatic, or prostate cancer (Gleason score ≥7) had positive BRCA1 or BRCA2 mutation, too. In multivariate analysis, the impact of younger age on mutation rates was considered insignificant (OR: 1.86; 95%CI: 0.89-3.91; p=0.10). However, breast cancer diagnosis at any age with 2 or more close relatives with breast cancer have is associated with a significantly higher BRCA mutation rate (OR: 2.76; 95%CI: 1.13, 6.71; p = 0.03). Conclusions: Arab patients with triple-negative breast cancer subtype have very high BRCA1 or BRCA2 mutation rates. Family history of breast cancer in close relatives further increase this risk.

Citation Format: Hikmat Abdel-Razeq, Lama Abujamous, Rayan Bater. High rates of BRCA1 and BRCA2 germline mutations among Arab patients with 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 PS8-34.
Abstract PS9-44: Breaking the silent struggles: Development of a cancer caregiver support program
Authors: Koerber Joyce Marie , Solti Magdolna
Published: February 2021

Background/Purpose: 4.6 million Americans serve as unpaid caregivers for someone with cancer. The burden of caregiving poses challenges to one’s physical, psychological, financial and spiritual health. Our project aimed to explore caregiver needs and provide comprehensive information and practical guidance to enhance coping during and after treatment. Methods: We conducted targeted interviews with 50 caregivers of patients with high risk cancers (brain, head and neck, lung, gastrointestinal, gynecologic, breast and hematologic cancers) to prioritize and discuss their most pressing concerns. Caregiver quality of life and well-being was assessed using validated tools that were measured at baseline and 6 months later. A Caregiver Resource Manual was developed with a list of tangible resources and provided to all families. Supportive interventions included counseling, palliative care, referral to nutrition and support groups.

Results: The interviewed caregivers included spouses, children, friends and parents. At baseline, 55% of patients had stage IV disease. Within 6-months, 38% of patients expired or progressed, 59% stayed in remission or remained stable on treatment. At baseline, 65% of caregivers reported moderate/high distress, 39% scored moderately/high in feeling their life was imposed upon, and 58% scored moderately/high in difficulty meeting their own medical needs. After intervention, moderate/high scores improved by 25% in distress, 18% in feeling life was imposed upon and 12% in attending to medical needs. The well-being survey found an 8% increase in all aspects assessed.Conclusion: Our project recognized patients and caregivers as one unit of care with information and support needed for both. The interventions improved caregiver stress and overall well-being. We found a gap in adequately preparing families for progressive nature of disease highlighting the need for proactive palliative care in the future.

Citation Format: Joyce Marie Koerber, Magdolna Solti. Breaking the silent struggles: Development of a cancer caregiver support program [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 PS9-44.
Abstract PS9-56: High compliance with choosing wisely breast procedures at a safety net hospital
Authors: Tang Annie , Mooney Colin , Ugarte Shannon , Knopf Kevin , Khoury Amal
Published: February 2021

The Choosing Wisely campaign has emerged recently in setting guidelines for surgical procedures of low utility and cost-ineffectiveness. Hospitals caring for underserved medical populations represent a unique opportunity to assess for quality of care and adherence to these guidelines. The Choosing Wisely campaign for breast surgery has highlighted: avoiding surgical re-excision for invasive cancer close to margins of excised breast tissue, avoiding double mastectomy in patients who have a single breast with cancer, avoidance of axillary lymph node dissection in women undergoing lumpectomy with limited nodal disease, and avoiding sentinel lymph node biopsy in patients ≥ 70 years of age with early stage breast cancer. Recent studies have shown variable adherence to these recommendations. In order to evaluate cost-effective surgery at our hospital serving a poorer patient population, we retrospectively analyzed patients who underwent surgery for breast cancer from 2015-2020. A total of 231 patients were identified. There were no patients who underwent re-excision for close margins of invasive cancer. Only 0.9% of patients (2/231) received contralateral mastectomy and only 1.6% of eligible patients (3/191) received axillary lymph node dissection instead of sentinel lymph node biopsy. Although 77.7% of patients ≥ 70 years of age with stage 1 hormone positive breast cancer (14/18) received sentinel lymph node biopsy, there was a downward trend during 2015 to 2020 from 100% to 50% of eligible patients receiving sentinel lymph node biopsy. De-implementation of traditional surgical practices, deemed as low-value care, towards newer cost-effective guidelines are achievable even at community hospitals serving a low socioeconomic community while preserving patient outcome and avoiding overtreatment. By avoiding overtreatment, cost savings can be achieved which allow for social distributive justice amongst breast cancer patients by ensuring careful utilization of scarce health economic resources.

Citation Format: Annie Tang, Colin Mooney, Shannon Ugarte, Kevin Knopf, Amal Khoury. High compliance with choosing wisely breast procedures at a safety net hospital [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 PS9-56.
Abstract SP114: Body Image and Sexual Health
Authors: Partridge A
Published: February 2021

Attention to body image and sexual health after breast cancer are important components of treatment decisions, support through treatment and survivorship care. A high proportion of breast cancer survivors report dissatisfaction with their physical appearance. Body image issues are particularly common among women who undergo mastectomy with or without reconstructive surgery and those who experience weight gain, hair loss from chemotherapy, and other psychosocial issues. Scalp cooling, proactive counseling about potential effects of treatment on weight and physical activity, and psychosocial support through treatment may help to prevent some of these negative effects. Weight loss and subsequent weight maintenance are notoriously difficult to achieve through diet alone, and exercise plays an important role in energy balance through and after treatment. Sexual health is frequently a concern for breast cancer survivors as well, with up to 40% of women reporting issues with sexual interest and 60% with physical sexual function. Issues may arise in the short term following both surgery and chemotherapy, due to factors including lower perceived attractiveness and vaginal dryness. Endocrine therapy with tamoxifen, aromatase inhibitors, and treatment-related amenorrhea or ovarian suppression treatment in premenopausal women are associated with sexual dysfunction. However, a multi-prong approach has been shown to improve such problems. Providers should actively monitor for and manage the consequences of diagnosis and treatment on body image and sexual health in survivors, using psychosocial, behavioral, and pharmacologic tools as needed.

Citation Format: A Partridge. Body Image and Sexual Health [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 SP114.
Abstract SP159: EMT
Authors: Yang J
Published: February 2021

During metastasis, epithelial tumor cells dissociate from each other, disseminate into the systemic circulation, and then establish secondary tumors in distant sites. A developmental program termed Epithelial-Mesenchymal Transition (EMT) is implicated in promoting the dissemination of single carcinoma cells during metastasis. Our recent studies aim to understand how EMT is dynamically regulated in response to signals from the tumor microenvironment and from the intracellular machineries to impact EMT and tumor metastasis. Specifically, I will present a mechanotransduction pathway that senses and transmits mechanincal cues from stiff matrix in the tumor microenvironment to promote EMT and invasion during tumor progression. Breast tumors are often detected due to their apparent “hardness” compared to normal tissues, and increasing matrix stiffness correlates with distant metastasis and poor survival in breast cancer patients. These observations raise the question of how mechanical forces generated by the rigid tumor ECM impact tumor progression and metastasis. In a hydrogel coupled with 3D Matrigel overlay culture system that recapitulates the range of physiological stiffness from normal mammary glands to breast tumors, increased ECM stiffness triggers Epithelial-Mesenchymal Transition (EMT), invasion and metastasis. We previously reported that the transcription factor Twist1 is an essential mechano-mediator that promotes EMT and metastasis in response to ECM stiffness. High matrix stiffness promotes Twist1 nuclear localization through phosphorylation-dependent regulation of its interaction with cytoplasmic anchor G3BP2. Using kinase screening and protein affinity purification, we identified a novel mechanoresponsive protein complex including an ephrin receptor and a Src-family kinase that promotes Twist1 phosphorylation and subsequent nuclear translocation in response to high matrix rigidity. Pharmacological and genetic inhibition of this mechanotransduction pathway blocks ECM stiffness-induced EMT and invasion in vitro and inhibits metastasis in human breast tumor xenografts. Our findings reveal a novel mechanotransduction pathway that responds to mechanical signals from the tumor microenvironment to drive EMT, invasion, and metastasis.

Citation Format: J Yang. EMT [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 SP159.
Abstract SP161: Context-dependent functions and inter-tumoral heterogeneity of tumor-associated myeloid cells.
Authors: Zhang X
Published: February 2021

Tumor-associated myeloid cells, including macrophages (TAMs) and neutrophils (TANs) have been extensively studied. Their pleotropic roles were observed in multiple steps of tumor progression and metastasis, and sometimes appeared to be inconsistent across different studies. In this talk, we will discuss evidence supporting the mutual influence between cancer cells and TAMs/TANs. We will review the immunosuppressive roles of these myeloid cells as well as their direct interactions with cancer cells. We will stress an emerging theme in recent studies: the precise myeloid functions may be determined by multiple factors including plasticity of these cells, mutual cooperation/competition among different cell types, and co-evolution between immune microenvironment and cancer traits. These factors together contribute to the heterogeneity of immune cells across tumors, an additional layer of heterogeneity beyond tumor-intrinsic characteristics.

Citation Format: X Zhang. Context-dependent functions and inter-tumoral heterogeneity of tumor-associated myeloid cells. [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 SP161.
Abstract SP031: Mechanisms of therapeutic resistance in ER+ breast cancer
Authors: Clarke RB
Published: February 2021

ER+ breast cancer is often successfully treated with endocrine therapies and more recently CDK4/6 inhibitors. In order to discover resistance mechanisms, we studied the tumour cells that survive anti-estrogen therapies such as tamoxifen and fulvestrant. We found that tamoxifen and fulvestrant therapy-resistant cells have cancer stem cell (CSC) attributes such as aldehyde dehydrogenase (ALDH) enzyme activity, mammosphere colony formation ex vivo and tumour initiation in vivo. We established that these CSC activities are regulated by pathways downstream of JAGGED/NOTCH4 receptor, the interleukin (IL) 1beta/IL1 receptor, and IL6/STAT3 signalling. Emerging data implicate these signalling pathways in metastatic progression, and both endocrine and CDK4/6 inhibitor therapy resistance. Targeting them in combination with current therapies has the potential to improve clinical outcomes.

Citation Format: RB Clarke. Mechanisms of therapeutic resistance in ER+ 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 SP031.
Abstract SP033: How and when to use immunotherapy and related toxicities
Authors: Cortes J
Published: February 2021

Targeting the immune system is an active therapeutic approach for a subgroup of patients with metastatic triple negative breast cancer (TNBC). In a breast cancer subtype in which new treatment strategies are greatly needed, the medical community welcomes this progress with great excitement. Single-agent anti PD-L1 and PD1 monoclonal antibodies have been evaluated in patients with locally advanced or metastatic TNBC. Although very limited efficacy was achieved in pre-treated patients, 1 out of 4 patients achieved an objective response when treated in the first-line setting. Of interest, many of these responses were long lasting. In 2019, atezolizumab was approved in combination with nab-paclitaxel in patients with metastatic TNBC whose tumors are positive for PD-L1 expression (≥1%) on immune infiltrate, evaluated by the VENTANA PD-L1 (SP142) antibody. However, when combined with paclitaxel, atezolizumab does not improve neither progression-free survival nor overall survival. On the other hand, pembrolizumab in combination when paclitaxel, nab-paclitaxel or carboplatin + gemcitabine has improved progression-free survival when PD-L1 expression was 10 or more (CPS score) evaluated by the 22C3 antibody. Unfortunately, the optimal platform to assess PD-L1 status is unknown, as it is the optimal cut-off value. Other biomarkers, such as mutational tumour burden or tumour infiltrating lymphocytes are not ready to be used in the clinic yet. Thus, biomarkers that can identify a broader group of patients who could benefit from this approach are urgently needed. Also, the combination of different immune checkpoint inhibitors between them or with other drugs, such as targeted therapy, may expand immunotherapy indication to more patients. Immune-related toxicities are closely associated with the known mechanisms of action of both PD-1 and PD-L1 antibodies, after restarting the anticancer immune system. The overall incidence is about 22% for all grades and 4% for high grades, being more frequent for patients treated with anti-PD-1 (all grades 27%) compared with anti-PD-L1 (all grades 17%). The most frequent organ specific immune-related adverse events were the endocrine system (7%), skin (5%), pulmonary system and gastrointestinal tract (4% each). Of note, immune-related deaths were reported in 0.34% of patients, the vast majority due to pneumonitis. When combined with chemotherapy, non-immune-related toxicities were reported with the same frequency as with chemotherapy alone.

Citation Format: J Cortes. How and when to use immunotherapy and related toxicities [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 SP033.
Abstract SP054: Obesity and Breast Cancer: Body Composition, Metabolic Mediators and Inflammation
Authors: Goodwin P
Published: February 2021

Obesity has been associated with an increased risk of postmenopausal breast cancer (predominantly ER+), as well as triple negative premenopausal breast cancer. It has also been associated with an increased risk of breast cancer distant recurrence and death, regardless or menopausal status or IHC defined breast cancer subtype. Obesity effects on recurrence and death are modest, with HRs for either outcome approximating 1.3. Obesity is linked to metabolic alterations that include insulin resistance (with associated high insulin and reduced glucose tolerance), altered lipids and adipokines, hypertension, central obesity, inflammation and increased risks of type 2 diabetes (T2DM) and cardiovascular disease - this constellation of attributes comprises the insulin resistance or metabolic syndrome. There is growing appreciation that BMI [weight (kg)/height (m)2] ≥ 30 kg/m2 is an imperfect measure of both body composition and underlying metabolic status. Recent research has focused on body composition (e.g. central obesity/sarcopenic obesity) and metabolic health (“healthy” obese, “unhealthy” normal weight) as predictors of breast cancer outcomes. Many of the inter-related physiologic changes associated with obesity (including higher levels of insulin, glucose, altered adipokines and, less consistently, circulating inflammatory factors) have individually been associated with increased breast cancer risk and/or poor breast cancer outcomes. These circulating factors, and obesity per se, have, in turn, been associated with changes in breast tissue and tumor micro-environment, including crown-like structures (dying adipocytes surrounded by inflammatory cells) as well as increased infiltration of inflammatory cells, cytokines and chemokines - all of which have been linked to cancer risk and progression in preclinical and/or clinical research. Evidence linking obesity/body composition, circulating obesity-associated physiologic and inflammatory factors to breast cancer outcomes will be discussed as will interventions (notably weight loss, metformin) targeting these factors in breast cancer patients. Recent findings linking breast inflammation to obesity/obesity-associated physiology and breast cancer outcomes will be reviewed. The inter-relatedness of these factors and the likelihood that the breast cancer-obesity link is complex and multifactorial will be highlighted.

Citation Format: P Goodwin. Obesity and Breast Cancer: Body Composition, Metabolic Mediators and Inflammation [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 SP054.
Abstract SP083: Treatment of HER2-positive metastatic breast cancer - advances and challenges
Authors: Lin N
Published: February 2021

Over the past two decades, there have been tremendous advances in treatment options for patients with HER2+ metastatic breast cancer (MBC). Median overall survival (OS) in control arm of the pivotal trastuzumab + chemotherapy study (Slamon et al, NEJM 2001) was 20.3 months. By contrast, median OS in the taxane/trastuzumab/pertuzumab arm of the CLEOPATRA trial was approximately 5 years, with an 8-year landmark OS of 37% (Wong et al, Oncologist 2019). Notably, OS improvements have also been demonstrated in the pivotal trials of ado-trastuzumab emtansine, tucatinib/capecitabine/trastuzumab, and trastuzumab deruxtecan in pre-treated patients with HER2+ MBC, such that we expect that median OS will only continue to lengthen. Indeed, with current therapies, a subset of patients can survive a decade or longer. Despite these improvements, there is still much progress to be made. First, the problem of brain metastases continues to contribute substantial morbidity and mortality in at least half of patients. While there have been advances in local therapy for brain metastases, breakthroughs in systemic therapy and prevention strategies ultimately will be needed to truly tackle this problem. Second, drug resistance nearly always appears over time, yet our understanding of HER2-resistance remains woefully incomplete. Developing a deeper understanding of therapeutic resistance may uncover novel targets that allow for more effective and durable treatment. Finally, with multiple highly active drugs now available, is it now time to pivot to testing curative-intent approaches in HER2+ MBC, particularly in those patients who present with de novo stage IV disease.

Citation Format: N Lin. Treatment of HER2-positive metastatic breast cancer - advances and challenges [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 SP083.
Abstract SP094: DCIS - Con
Authors: McLaughlin S
Published: February 2021

Ductal carcinoma in situ (DCIS) represents a collection of biologically heterogenous pre-invasive breast lesions some with the potential for progression to invasive cancer. Widespread adoption of screening mammography has increased the diagnosis of DCIS and may contribute to overdiagnosis identifying some conditions that may never impact one’s overall health. Unfortunately, clinicians treating DCIS patients currently lack robust biomarkers stratifying DCIS patients into those at high or low risk for invasive progression. Further, variations in pathologic assessment and grade, intra-lesional DCIS heterogeneity, and discordance in pathologic interpretations between pathologists make it challenging for providers to further identify appropriate low risk DCIS patients for active surveillance. Guideline concordant care including excision and potentially radiation and anti-estrogen therapies should remain as the standard of care and provides a definitive treatment endpoint which patients desire. Existing evidence documents a significant upstage rate of DCIS to invasive disease at surgical excision including a small, but important population benefiting from adjuvant systemic therapy. Finally, patient anxiety and documented poor adherence rates to endocrine therapy preclude active surveillance and after all the morbidity of surgical excision is low.

Citation Format: S McLaughlin. DCIS - Con [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 SP094.
Ultrasound Biomicroscopy Documented Anterior Uveal Melanoma Regression after Ruthenium-106 Plaque Therapy
Authors: Kuzmanović Elabjer Biljana , Bušić Mladen , Pleše Andrej , Bjeloš Mirjana , Miletić Daliborka , Vukojević Nenad
Published: February 2021

Introduction: Ultrasound biomicroscopy (UBM) is the only widely used method for the evaluation of anterior uveal melanoma (AUM). Objective: Documentation of regression of AUM treated with ruthenium-106 (Ru-106) plaque types CCB and CCC using UBM. Methods: This single institution-based retrospective case series involved 10 Caucasian patients with AUM followed after brachytherapy with UBM from January 2014 until February 2019. The largest prominence of the tumor perpendicular to the sclera or the cornea (including scleral/corneal thickness) (D) and the largest basal dimension (B) were measured in millimeters with UBM for all patients prior to the brachytherapy and at 4-month interval follow-up. Tumor regression was calculated as a percentage of decrease in the initial D and B values. Results: The study involved 10 patients with a mean age of 64.4 years (yr) (range 46–80 yr). D ranged from 1.82 to 5.5 mm (median 2.99 mm) and B from 2.32 to 12.38 mm (median 4.18 mm). The apical radiation dose in all patients was 100 Gy. The median follow-up was 42.02 months. Regression for D was 21.11 ± 13.66%, 31.09 ± 14.66%, and 34.92 ± 19.86% at 1st, 2nd, and 3rd year of the follow-up, respectively, while for B it was 21.58 ± 16.05%, 28.98 ± 17.71%, and 32.06 ± 18.96%, respectively. Tumor recurrence was documented in 2/10 patients. Conclusion: The major regression of AUM, treated with Ru-106 plaque types CCB and CCC, was documented in the first 2 years after brachytherapy in our study group. In the following years, only minimal regression was documented that warns of the need for close monitoring and active search for local recurrences.
Transcranial Direct Current Stimulation Combined with Botulinum Neurotoxin Type A Injections for Treatment of Upper Limb Intention Tremor in Multiple Sclerosis: A Case Report
Authors: Facciorusso Salvatore , Spina Stefania , Santoro Luigi , Cinone Nicoletta , Baricich Alessio , Ciritella Chiara , Fiore Pietro , Santamato Andrea
Published: February 2021

Upper limb intention tremor is a common cause of disability in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) is an emerging form of brain stimulation used to improve sensorimotor impairments in many neurological disorders. Here, we describe a combined therapeutic approach with botulinum neurotoxin type A (BoNT-A) and tDCS for the treatment of upper limb tremor in a patient with MS. We administered a cathodal tDCS 15 days after the injections of BoNT-A. Both post-injection and post-stimulation evaluation revealed a considerable improvement of the tremor. This approach positively affected the patient’s activities of daily living. Our case report shows a safe and beneficial effect of tDCS in the treatment of action tremor in MS especially as a possible adjunctive synergic treatment with BoNT-A injections.
Immune System Efficiency in Cancer and the Microbiota Influence
Authors: Barbosa Ana Margarida , Gomes-Gonçalves Alexandra , Castro António G. , Torrado Egídio
Published: February 2021

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.