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Despite evidence that early-stage male breast cancer (MBC) can be treated the same as in females, we hypothesized that men undergo more extensive surgery.Patients with clinical T1-2 breast cancer were identified in the National Cancer Database 2004-2016. Trends in surgery type and overall survival were compared between sexes.Of 9,782 males and 1,078,105 females, most were cN0 with AJCC stage I/II disease. Unilateral mastectomy was most common in men (67.1% vs. 24.1%, p 0.001) and partial mastectomy in women (64.7% vs. 26.4%, p 0.001), with no significant change over time. Over 1/3 of men received ALND in 2016. While overall survival was superior in females (HR 0.83, 95% CI 0.73-0.94, p = 0.003), partial mastectomy was associated with a 42% reduction in mortality risk for males (HR 0.58, 95% CI 0.4-0.8, p = 0.003).De-escalation of surgery could be considered for MBC to improve survival and align with current standards of care.

PDF file, 1661K, Supplemental Figure S1- Chemical Structures. Supplemental Figure S2-Oxygen Consumption in MCF-7 Cells treated with or without betalapchone and dicoumarol. Supplemental Figure S2 legend. Supplemental Figure S3-Survival assay for normal mammary epithelial cells treated with betalapachone with or without dicoumarol. Supplemental Figure S3 legend. Supplemental Figure S4-Survival assay for MDA-MB231 cells treated with or without quinones and ROS scavengers. Supplemental Figure S4 legend. Supplemental Figure S5-Westernblot of MCF-7 cells treated with betalapachone with or without catalase. Supplemental Figure S5 legend. Supplemental Figure S6-Proteolysis of PARP in MCF-7 cells treated with betalapachone or staurosporine. Supplemental Figure S6 legend. Supplemental Figure S7- NQO1 mediated futile cycle of betalapachone. Supplemental Figure S7 legend. Supplemental Figure S8- Western blot and analysis of NQO1 to Catalase ratios in Breast Cancer Cell lines. Supplemental Table 1- NQO1 enzymatic activity in breast cancer cell lines. Supplemental Table 1 legend.

BackgroundCardiovascular disease (CVD) is the leading cause of death in men with prostate cancer (PC). Accumulated stress plays an important role in CVD development. The cumulative burden of chronic stress and life events can be measured using allostatic load (AL).MethodsThe initial cohort included males aged 18 years and older diagnosed with PC (2005-2019). AL was modeled as an ordinal variable (0-11). Fine-Gray competing risk regressions measured the impact of precancer diagnosis AL and postdiagnosis AL in 2-year major cardiac events (MACE). The effect of AL changes over time on MACE development was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after PC diagnosis).ResultsWe included 5261 PC patients of which 6.6% had a 2-year MACE. For every 1-point increase in AL before and within 60 days after PC diagnosis, the risk of MACE increased 25% (adjusted hazard ratio [aHR] =1.25, 95% confidence interval [CI] = 1.18 to 1.33) and 27% (aHR = 1.27, 95% CI = 1.20 to 1.35), respectively. Using AL as a time-varying exposure, the risk of MACE increased 19% (aHR = 1.19, 95% CI = 1.11 to 1.27), 22% (aHR = 1.22, 95% CI = 1.14 to 1.33), 28% (aHR = 1.28, 95% CI = 1.23 to 1.33), and 31% (aHR = 1.31, 95% CI = 1.27 to 1.35) for every 1-point increase in AL before, 2 months after, 6 months after, and 1 year after PC diagnosis, respectively.ConclusionAL and its changes over time are associated with MACE in PC patients, suggesting a role of a biological measure of stress as a marker of CVD risk among men with PC.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a higher risk of locoregional and distance recurrence. Consequently, this population was considered poor candidate for breast conservation (BCT). Our study aim was to determine whether BCT plus radiotherapy (RT) was equivalent to mastectomy for TNBC after adjustment of selection bias of demographic and clinical characteristics. Methods: The National Cancer Database was queried for women diagnosed as primary unilateral invasive clinical T1-2N0-2 TNBC from 2004-2016. Patients who underwent mastectomy or breast conservation (partial mastectomy plus radiation) were included. A 1:1 propensity match with replacement was performed to compare breast conservation vs. mastectomy. Overall survival was analyzed using stratified multivariable Cox proportional hazard regression analysis.Results: Of 59,599 clinical T1-2N0-2 TNBC patients, 26,325 (44.2%) underwent mastectomy and 33,274 (55.8%) were treated with BCT. BCT patients were older (median age 59 vs. 54, p Citation Format: Lifen Cao, Christopher W Towe, Megan E Miller, Alberto J Montero, Robert Shenk. Breast conservation plus radiotherapy provides superior survival benefit than mastectomy in triple negative breast cancer: A propensity matched national cancer database analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-02.

It was suggested that stereotactic radiation (SBRT) is an "alternative if no surgical capacity is available" for non-small cell lung cancer (NSCLC) care during the COVID-19 pandemic. The purpose of this study was to compare the oncologic outcomes of delayed surgical resection and early SBRT among operable patients with early stage lung cancer.The National Cancer Database was queried for patients with cT1aN0M0 NSCLC who underwent surgery or SBRT (2010-2016) with no comorbidity. Patients with any comorbidities or age80 were excluded. The outcome of interest was overall survival. Delays in surgical care were modeled using different times from diagnosis to surgery. A 1:1 propensity match was performed and survival was analyzed using multivariable Cox regression.Of 6720 healthy cT1aN0M0 NSCLC patients, 6008 (89.4%) received surgery and 712 (10.6%) received SBRT. Among surgery patients, time to surgery30 d was associated with inferior survival (HR 1.4, P ≤ 0.013) compared with patients receiving surgery ≤14 d. Relative to SBRT, surgery demonstrated superior survival at all time points evaluated: 0-30 d, 31-60 d, 61-90 d, and90 d (all P 0.001). Among a propensity-matched cohort of 256 pairs of patients, delayed surgery (90 d) remained association with better overall survival relative to early SBRT (5-year survival 76.9% versus 32.3%, HR = 0.266, P 0.001).Although longer time to surgery is associated with inferior survival among surgery patients, delayed surgery is superior to early SBRT. Surgical resection should remain the standard of care to treat operable early stage lung cancer despite delays imposed by the COVID-19 pandemic.

Race, access to care, and molecular features result in outcome disparities in triple-negative breast cancer (TNBC). We sought to determine the role of age in TNBC disparity by hypothesizing that younger patients receive more comprehensive treatment, resulting in survival differences.The National Cancer Database was used to identify women with unilateral TNBC treated from 2005 through 2017. Patients were stratified by age (≤40, 41-70,70); demographics, clinical characteristics, and treatment factors were compared. Logistic regression determined factors associated with treatment received. Survival outcomes were analyzed using a stratified log-rank test.Of the 168,715 patients, 16,287 (9.6%) were ≤40 years. Patients ≤40 were significantly more likely to present at higher clinical stage (P.001) and receive neoadjuvant chemotherapy (NAC, P.001). Bilateral mastectomy was the most common surgery for patients ≤40 (37%), whereas partial mastectomy was most often used in patients 41 to 70 years old (48%) and those70 (49%) (P.001). Patients ≤40 years were significantly more likely to undergo both NAC and mastectomy than those40 (odds ratio 1.5, both P.05) despite a greater in-breast tumor response in the youngest patients. Patients treated with mastectomy and axillary lymph node dissection had inferior survival outcomes compared to those treated with partial mastectomy and sentinel lymph node biopsy across all 3 age groups (P.001).The clinical characteristics of TNBC differ significantly at the extremes of age, likely driving treatment decisions. Although patients ≤40 present with a more advanced disease and appropriately receive NAC, they also undergo more extensive surgery that does not yield a survival benefit. Further research is needed to determine if age disparity is due to oncologic factors or patient and provider preferences.

Purpose: Approximately 20% of all breast cancers (BC) are HER2 amplified. In the APT trial, weekly paclitaxel/ trastuzumab in node negative HER2+ BC with tumors Methods: In the National Cancer Database (2004-2017), patients with a primary diagnosis of pT1N0M0 HER2+ BC, were separated into two groups: (i) HER2 monotherapy, i.e. trastuzumab, and (ii) chemo-HER2 therapy. A 3:1 propensity match was performed to balance patient selection bias between the two different cohorts. Long-term overall survival (OS) was compared between both groups. Results: A total of 23, 281 patients met the criteria. 22,268 (96.7%) received chemo-HER2 therapy and 1,013 (4.4%) received HER2 monotherapy. Propensity match identified 1,995 patients who received chemo-HER2 therapy, and 666 who received HER2 monotherapy. After match, adjuvant chemo-HER2 therapy was associated with a modest survival advantage over HER2 monotherapy (5-year OS 94.1% vs. 90.6%, P=0.041). Conclusions: Even though there is a modest OS advantage favoring adjuvant chemo-HER2 therapy in pT1N0 HER2+ BC, HER2 monotherapy was associated with 5-year OS >90%. Therefore, in select patients who have contraindications for cytotoxic chemotherapy, or decline adjuvant chemotherapy, adjuvant trastuzumab monotherapy appears to be a reasonable alternative.

Background: Routine sentinel lymph node biopsy (SLNB) has been recommended against by Choosing Wisely© Foundation due to its low value in clinical node negative, hormone receptor positive breast cancer patients age≥70 years old. We used the National Cancer Database (NCDB) to examine the effect of SLNB omission and outcomes in this population. We hypothesized that SLNB would be beneficial in this population.Methods: The National Cancer Database was queried for women diagnosed with primary unilateral invasive clinical stage T1N0M0 hormone receptor positive, HER-2 negative breast cancer from 2012-2017. Patients age ≥ 70 years old with Charlson Score ≥1 who underwent partial mastectomy and received hormonal therapy were included in the study cohort. Patients received neoadjuvant therapy or underwent upfront axillary lymph node dissection (ALND) were excluded. A 1:3 propensity match with replacement was performed to compare SLNB omission vs. SLNB group controlling age, race, comorbidities, insurance and facility. Overall survival was analyzed using stratified multivariable Cox proportional hazard regression analysis.Results: Of 14,150 patients, 1,928 (13.6%) omitted SLNB and 12,222 (86.4%) underwent SLNB, including 1,545/12,222 (12.6%) who proceeded to ALND. Central portion tumor location (OR=1.77, P=0.001), clinical T1c (OR= 2.49, P Citation Format: Lifen Cao, Megan E Miller, Luke D Rothermel, Alberto J Montero, Christopher W Towe, Robert Shenk. Less is not necessarily more: A propensity matched national analysis on effect and outcome of sentinel lymph node biopsy omission [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-08.

Neoadjuvant chemotherapy (NAC) downstages breast cancer and provides prognostic information. Males with breast cancer are known to receive less treatment overall and have poorer outcomes relative to females. We hypothesized that males would be less likely to receive NAC. Patients with a primary diagnosis of cN1–3 breast cancer were identified in the National Cancer Database (2004–2016). Multivariable logistic regression determined the association between NAC utilization and sex, and the relationship between sex and NAC response, controlling for demographic and tumor factors. Overall survival was analyzed using a multivariable Cox model. In total, 196,027 patients (194,010 females, 2017 males) met inclusion criteria. A significantly greater proportion of males underwent mastectomy (80% vs. 60%, P < 0.001), and axillary lymph node dissection (76% vs. 74%, P = 0.022). Overall fewer men received chemotherapy than women (73% vs. 84%, P < 0.001); men also received NAC at a significantly lower rate (26% men vs. 45% women, P < 0.001). After accounting for demographic and oncologic factors including hormone receptor (HR) subtype, females remained more likely to undergo NAC (OR 1.84, P < 0.001). On multivariable analysis, sex was not associated with pathologic response or overall survival after NAC. Although oncologic outcomes after NAC were similar, males with node-positive breast cancer received less NAC and more aggressive surgery than females. These data suggest men achieve outcomes comparable to women with cN1–3 disease, and NAC should be used in appropriate male patients to downstage the breast and axilla.

Background Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. Methods Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010–2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). Results Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson–Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. Conclusions Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10459-3.

543 Background: Early validation studies using the Oncotype DX recurrence score (RS) in NSABP B20 demonstrated that women with node negative breast cancer and RS >31 had significant survival benefit from the addition of adjuvant chemotherapy to endocrine therapy (CET). Consequently, in the prospective TAILORx trial, node negative women with RS >26 received CET. These studies did not clearly delineate the magnitude of benefit of adjuvant chemotherapy for post-menopausal node negative women. A recently published well-designed adjuvant trial (RxPONDER) demonstrated that adjuvant chemotherapy was not beneficial in post-menopausal pts with ER+/HER2- breast cancer, 1-3 positive nodes, and RS 26 compared to endocrine therapy (ET) alone, given that CET is more beneficial in women 50 with ER+/HER2- pT1-2N0M0 breast cancer with RS >26, to assess real world utilization. We separated women into two groups based on adjuvant treatment: ET alone or CET. Chi-square and logistic regression analysis determined difference between different systemic treatment groups. OS was analyzed using a multivariable Cox model. Results: A total of 16,745 eligible women who underwent surgery and received ET were identified in the NCDB—4,740 (28.3%) received ET alone and 12,005 (71.7%) received CET. We observed that CET use increased over time. Women were more likely to receive CET if their tumors were moderately differentiated (OR = 1.853, p < 0.001), poorly/undifferentiated tumors (OR = 3.875, p < 0.001), or associated with lymph-vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5-year OS rates in this cohort were significantly superior in women receiving CET compared to ET alone (95.4% vs 92.0%, Hazard Ratio = 0.680, p < 0.001). Conclusions: Utilizing the NCDB to represent real world outcomes, we observed that women > 50 years with pT1-2N0M0 ER+/HER2- breast cancer, and RS > 26 had a significantly superior 5-year OS when receiving adjuvant chemotherapy provides a measurable OS benefit for post-menopausal women in this setting and should be discussed with patients.

540 Background: Based on the results of the RxPonder trial, post-menopausal women over age 50 with estrogen receptor (ER)+ breast cancer, 1-3+ nodes, and a 21-gene Oncotype DX recurrence score (RS) score of 20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age < = 50: HR = 0.334, P = 0.002; age > 50: HR = 0.521, P = 0.019). Conclusions: Among women with ER+/HER2- breast cancer with 1–3 positive nodes, and RS of 20-25, in contrast to the RxPonder trial we observed that CET was associated with an OS benefit in women regardless of age.

TPS10618 Background: Coronavirus disease 2019 (COVID-19), caused by betacoronavirus SARS-CoV-2, is associated with an increased risk of severe infection or death in cancer patients compared to the general population. The CANVAX trial recently demonstrated that short term immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer— particularly those who receive myelosuppressive chemotherapy. Because little is known regarding longitudinal antibody or T-cell responses in cancer patients who receive cytotoxic chemotherapy or non-myelosuppressive targeted systemic therapy, the aim of this longitudinal study is to assess immune B and T cell responses to SARS-CoV-2 over a 12-month period in solid tumor patients who receive chemotherapy or non-immunosuppressive therapy compared to healthy individuals without cancer. Methods: This is an ongoing prospective non-interventional clinical trial (NCT05238467). Approximately 100 patients will be enrolled into three different arms. Accrual began in May 2021 and 37 patients have been enrolled. Eligible patients must not have prior COVID-19 infection < 6 months from study enrollment and have a diagnosis of a solid tumor (breast, genitourinary, or gastrointestinal cancers), who either: received myelosuppressive chemotherapy within 60 days prior to initial or booster COVID vaccination, or who started on chemotherapy within 30 to 60 days after the initial or booster COVID vaccination (Arm A); or received non-immunosuppressive treatments (Arm B); or have no history of cancer or prior history of cancer but beyond 12 months from completion of curative cancer treatment (Arm C, control cohort). Whole blood will be collected in accordance with standard operating procedures. Blood samples analyzed for the presence of antibodies against the major antigenic components of SARS-CoV-2 including the spike glycoprotein (S), receptor binding domain (R) and nucleocapsid phosphoprotein (N). Antibody levels will be quantified utilizing quantitative ELISA. T-cell responses will also be quantified. The primary endpoint is seroprotection rate with an antibody titer protective (1:40) at any point: baseline, 2, 6, and 12 months. The secondary endpoint is to evaluate differences in longitudinal immunological responses to SARS-CoV-2 over a 12-month period. The difference of the seroprotection rate among 3 cohorts of participants will be examined using chi-square test. Moreover, the effect of treatment (chemotherapy, endocrine, TKIs) on seroprotection will be estimated using multivariable logistic regression controlling the effects of confounders, such as age, gender and cancer type. COVID antibody titers measured over time (baseline, 8 weeks, 6, 9, 12 months after the second vaccination) will be analyzed using mixed-effect models. Clinical trial information: NCT05238467.

Background Immune checkpoint inhibitors (ICI) and targeted therapies (TT) have improved the survival outcomes in patients with advanced melanoma. However, less is known about their impact on Asian patients with melanoma. In this study, we hypothesize that patients of Asian ancestry would have improved survival for advanced melanoma since the introduction of ICI and TT in 2011. Methods Asian patients with melanoma were identified in the National Cancer Database (NCDB) from 2004–2016. Patient, tumor, and treatment characteristics were compared for populations treated before and after 2011 using Chi-square analyses. Overall survival (OS) was analyzed using Kaplan-Meier estimates. Results 1,411 Asian patients with melanoma were identified. Overall, 21% were melanoma in situ, and 79% were invasive melanomas. 62% of patients did not have a documented histologic subtype. The most common reported histologies were superficial spreading (14%) and acral lentiginous (10%) melanomas. Primary locations included 41% lower extremity, 17% upper extremity, and 11% head and neck. The age at diagnosis has increased during the study period - 38% over 60 years old in 2004, to 54% in 2016 (P Conclusions Asian patients with melanoma are receiving diagnoses at older ages. Despite decreases in OS for all Asian patients with melanoma, advanced stage IV of the diseases have improved outcomes for the group treated in the era of ICI and TT. Further investigation is warranted to understand the treatment, patient, and tumor characteristics that predict response in this demographic of patients.

e13034 Background: Current ASCO guidelines recommend endocrine therapy as preferred primary treatment for hormone receptor positive (HR+) metastatic breast cancer (MBC). We assessed survival outcomes of HR+/HER2- MBC patients undergoing endocrine therapy with and without chemotherapy. Methods: The National Cancer Database was queried 2004-2016 for patients with de novo HR+/HER2- MBC. Exclusion criteria were treatment with surgery or radiation at the primary site and missing oncologic and follow up data. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression modes. Results: 19,317 patients met inclusion criteria, among whom 2,360 (12%) received no systemic therapy, 2,617 (14%) received chemotherapy only, 10,078 (52%) received endocrine therapy only and 4,262 (22%) received both chemotherapy and endocrine therapy. Patients treated with chemotherapy only more frequently had lung (38%, p

e21525 Background: Metastatic melanoma is an aggressive disease with a rapid systemic dissemination. We evaluated the effect of metastatic sites on the utilization immunotherapy and survival outcomes in stage IV melanoma. Methods: The National Cancer Database from 2010-2017 was queried for stage IV melanoma. Those with missing relevant data were excluded. Patients were grouped into five categories based on metastatic sites: lung metastasis only, brain metastasis only, liver metastasis only, bone metastasis only and multiple sites metastasis. Multivariable logistic regression was used to predict use of immunotherapy. Effects of immunotherapy on overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards model. Results: A total 12, 315 were included in the study, among whom 2206 (17.9%) had lung metastasis only, 1,873 (15.2%) had brain metastasis only, 785 (6.4%) had liver metastasis only, 662 (5.4%) had bone metastasis only and 5,983 (48.6%) presented with multiple metastatic sites. Surgery at primary site was performed in 34.3% of patients with bone metastasis (p

e13054 Background: Conflicting data exist regarding benefit of surgery of the primary site for stage IV breast cancer, in which systemic therapy is standard of care and patient characteristics may bias treatment decisions. Metastatic triple negative breast cancer (TNBC) is an aggressive subtype with limited therapy options and poor prognosis. Our aim was to assess whether surgery for the primary tumor in stage IV TNBC provides a survival advantage over systemic therapy alone. Methods: The National Cancer Database was queried for patients with de-novo stage IV TNBC who received systemic therapy alone or systemic therapy and surgery of the primary breast site 2004-2016. Patients receiving surgery for metastatic tumor sites or with incomplete follow up data were excluded. 1:1 propensity matching was performed for demographics, comorbidities, clinical T and N stage, and metastatic sites to minimize confounding factors. Survival outcomes were analyzed using a stratified log-rank test and Cox proportional hazard regression analysis. Results: Of 2989 patients, 782 (26.21%) underwent surgery plus systemic therapy and 2207 (73.84%) were treated with systemic therapy alone. The majority of all patients were aged 51-70 with low co-morbidity, and treated in metropolitan areas. Patients treated at academic facilities (OR = 0.67, p = 0.025), with multiple metastatic sites (OR = 0.59, p < 0.001), or advanced clinical N stage (OR = 0.55, p < 0.001) were less likely to undergo surgery. Of those who completed surgery, 58% had unilateral mastectomy, and 63% had axillary lymph node dissection. Propensity matching identified 507 ‘paired’ patients with similar characteristics in the surgery and systemic therapy alone groups. After multivariable adjustment, surgery was associated with superior overall survival compared with systemic therapy alone (HR 0.73, P < 0.001). Older age (HR = 1.47, p < 0.001), greater comorbidity (HR = 1.28, p < 0.001) and multiple metastatic sites (HR = 1.53, p < 0.001) significantly decreased overall survival in the matched cohort. Median survival was shortest in the systemic therapy alone group (12.8 months, 95% CI 11.3-14.5) and longest in those undergoing systemic therapy plus simple mastectomy (18 months, 95% CI 14.3-21.2), though approximately 4 months of median survival was added for all patients undergoing any surgery vs. systemic therapy alone (p = 0.0001). Conclusions: In stage IV TNBC, surgical resection of the primary tumor site in addition to systemic therapy may provide a survival benefit in selected patients. Though in this retrospective study the sequence of treatment was unknown, surgery could be considered for low disease burden as in other malignancies with oligometastatic disease. Additional research is needed to determine if these findings persist in prospective studies and for other hormone-receptor subtypes.

This study was aimed at investigating the potential of cell-free DNA (cfDNA) as a biomarker for colorectal cancer prognosis. Sixty patients with colorectal cancer who had not undergone surgery were enrolled as study group. Their peripheral blood samples were collected, and peripheral blood of 30 healthy volunteers (control) was collected. The cfDNA concentration and integrity were determined using q-PCR so as to ascertain if cfDNA was associated with clinical presentations of the disease. Then, the specificities and sensitivities of cfDNA, CFA and CA199 were determined with ROC curve. The level and integrity of cfDNA in patients with colorectal cancer before surgery were significantly higher than those in patients with colorectal cancer after surgery, and cfDNA concentration of colorectal cancer patients after surgery was also significantly higher than that in healthy control group. However, the integrity was not significantly different from that of control group. There was a significant correlation between cfDNA concentration and TNM stage, differentiation degree and CEA expression, while cfDNA integrity was significantly correlated with TNM stage and degree of differentiation. Moreover, specificity and sensitivity of cfDNA concentration and integrity were higher than those of CEA and CA199. The TNM stage and cfDNA concentration were independent risk factors for progression-free survival (PFS) in colorectal cancer patients. In conclusion, cfDNA concentration and integrity were more sensitive and specific than traditional tumor markers (CA199, CEA). Thus, changes in cfDNA changes can be effectively used to determine the prognosis of postoperative colorectal cancer patients.

Background: Male breast cancer has been less well studied due to the rarity of this condition compared with female breast cancer. Men have traditionally presented at later stages than women, leading to disparities in outcomes. Our aim was to identify the incidence of male breast cancer in recent years and determine trends in clinical and pathologic stage that could be utilized to improve breast cancer care. Methods: Patients diagnosed with primary breast cancer between 2004 and 2016 were identified using the National Cancer Database (NCDB), which collects hospital registry data from over 1,500 Commission on Cancer (CoC)-accredited facilities and represents more than 70% of newly diagnosed cancer cases in the United States. Patient, tumor, treatment, and facility data was compared between male and female patients. Incidence of male and female breast cancer was stratified by both AJCC clinical stage and pathologic stage (I-IV) and evaluated over the study period. Results: 17,814 male breast cancer patients and 2,001,551 female patients with breast cancer were identified. The incidence of male breast cancer increased by 1.5-fold from 1044 cases per year in 2004 to 1565 cases per year in 2016. The number of female breast cancer cases was 123,799 in 2004 and reached the highest annual volume of 184,718 in 2015. In 2010 incident male breast cancer cases rose by nearly 100% compared with the prior year, the majority of which represented early stage disease. In that year alone, for males there was a 99.6% increase (276 vs. 556 cases) in pathologic stage I disease, 89% increase (200 vs. 378 cases) in pathologic stage II disease and 94.7% increase (68 vs. 132 cases) in patients diagnosed with in situ disease. After 2010, incidence patterns for male breast cancer stabilized with ratio changes for Stage I or II at the level of only 1% to 7.3% per year. Interestingly, the proportion of male to female breast cancer incident cases remained constant over the study period, with males representing 0.8-0.9% of the total cases. Overall, a minority of patients presented with Stage III (6.6%) and Stage IV (4.6%) disease, though a greater proportion of males than females had advanced stage disease at diagnosis (16.88% of males vs. 11.14% females, p< 0.001). The incidence of clinical Stage I and II disease increased over time for both genders, though a greater proportion of female breast cancer was Stage I (43.2% female vs. 35.93% male, p Citation Format: Lifen Cao, Rashi Singh, Anuja L Sarode, Michael Kharouta, Robert Shenk, Megan E Miller. Trends in incidence and stage of male breast cancer, 2004-2016: An analysis from the national cancer database [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 PS14-10.

Introduction: Due to the low incidence of male breast cancer, large scale prospective trials to guide therapy are lacking. Historically males with breast cancer present at more advanced stages than females and have been surgically treated with modified radical mastectomy. Recent studies suggest that breast-conserving therapy for early-stage male breast cancer yields similar outcomes as for female patients, and that sentinel lymph node biopsy (SLNB) can be used in place of axillary lymph node dissection (ALND) for appropriate clinically node-negative patients. Our study investigates trends in breast and axillary surgery for male breast cancer patients, focusing specifically on the treatment of early-stage disease. Methods: The National Cancer Database (NCDB) was utilized to identify male and female patients diagnosed with clinical T1-2 breast cancer from 2004-2016. Patient, tumor, facility, and surgical treatment factors were examined. Patients were stratified by surgery type: partial, unilateral, and bilateral mastectomy; simple versus modified radical mastectomy; SLNB (removal of ≤ 5 lymph nodes) and ALND (>5 lymph nodes). Trends in surgery type were compared between male and female patients and over the study period for each gender. Results: 9,782 males and 1,078,105 females with T1-2 breast cancer were identified. Men were significantly older at diagnosis than women (31.4% vs. 23.6% age >70, p0). ER/PR+ disease (94.2% vs. 84.1%, p Citation Format: Rashi Singh, Lifen Cao, Anuja L Sarode, Michael Kharouta, Robert Shenk, Megan E Miller. Trends in breast and axillary surgery for T1-T2 male breast cancer: A study from the national cancer database [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 PS14-12.

A new process for preparation of porous acrylamide resins has been proposed. The process is that Al(OH) 3 obtained from the reaction of aluminum chloride and sodium bicarbonate in solution is cross-linked with acrylamide copolymer in copolymerization and then dehydrated and converted into γ-Al 2 O 3 at 142 °C. Therefore, lots of pores are generated in the acrylamide copolymer by means of water vapor released from the dehydration of Al(OH) 3 . The mesoporous structure of the copolymer is demonstrated by the scanning electronic microscope (SEM) and isothermal adsorption of nitrogen. Results show that one of the prepared porous acrylamide copolymers with a specific surface area ( A BET ) of 113.03 m 2 g −1 and an average pore size of 15.82 nm possesses excellent humidity control properties. It can maintain the relative humidity (RH) between 50% and 60% in 3.5 h at 25 °C and can present a maximum moisture content of 134% of its own weight. It also shows good buffering effect to RH fluctuation at changed ambient temperatures. This work provides useful information for preparing humidity control materials for museum, gallery display cases and artifacts transportation in particular.

A new consolidation system for fragile ancient silk fabrics by fibroin with the support of ethylene glycol diglycidyl ether (EGDE) was developed in our group. To figure out the mechanism and the effect of EGDE in the system, aged silk fabrics treated with EGDE have been investigated in this paper. Silk fabrics were artificially aged in sodium hydroxide aqueous solution to simulate fragile ancient silk fabrics. The aged silk fabrics were treated with EGDE aqueous solution by spraying. The resultant silk fabrics were systematically investigated by tensile test, thermogravimetric analysis (TGA), thermal ageing resistance test, attenuated total reflection Fourier transform infrared spectroscopy (ATR–FTIR), solid-state 13 C cross polarization/magic angle spinning nuclear magnet resonance ( 13 C CP/MAS NMR) and amino acid analysis (AAA), etc. Results indicate that the breaking stress and strain of the treated silk fabrics increase more than four and two times, respectively. The maximum decomposition temperature of the treated silk fabrics is much higher than that of the aged silk fabrics. The treated silk fabrics exhibit a better thermal ageing resistance than the aged silk fabrics. Chemical interactions occurred between EGDE and silk fibroin molecules in silk fabrics. This work provides useful information for the protection of historic silk fabrics.

Aims: β-Lapachone (β-lap), a novel radiosensitizer with potent antitumor efficacy alone, selectively kills solid cancers that over-express NAD(P)H:quinone oxidoreductase 1 (NQO1). Since breast or other solid cancers have heterogeneous NQO1 expression, therapies that reduce the resistance (e.g., NQO1low) of tumor cells will have significant clinical advantages. We tested whether NQO1-proficient (NQO1+) cells generated sufficient hydrogen peroxide (H2O2) after β-lap treatment to elicit bystander effects, DNA damage, and cell death in neighboring NQO1low cells. Results: β-Lap showed NQO1-dependent efficacy against two triple-negative breast cancer (TNBC) xenografts. NQO1 expression variations in human breast cancer patient samples were noted, where ∼60% cancers over-expressed NQO1, with little or no expression in associated normal tissue. Differential DNA damage and lethality were noted in NQO1+ versus NQO1-deficient (NQO1−) TNBC cells and xenografts after β-lap treatment. β-Lap-treated NQO1+ cells died by programmed necrosis, whereas co-cultured NQO1− TNBC cells exhibited DNA damage and caspase-dependent apoptosis. NQO1 inhibition (dicoumarol) or H2O2 scavenging (catalase [CAT]) blocked all responses. Only NQO1− cells neighboring NQO1+ TNBC cells responded to β-lap in vitro, and bystander effects correlated well with H2O2 diffusion. Bystander effects in NQO1− cells in vivo within mixed 50:50 co-cultured xenografts were dramatic and depended on NQO1+ cells. However, normal human cells in vitro or in vivo did not show bystander effects, due to elevated endogenous CAT levels. Innovation and Conclusions: NQO1-dependent bystander effects elicited by NQO1 bioactivatable drugs (β-lap or deoxynyboquinone [DNQ]) likely contribute to their efficacies, killing NQO1+ solid cancer cells and eliminating surrounding heterogeneous NQO1low cancer cells. Normal cells/tissue are protected by low NQO1:CAT ratios. Antioxid. Redox Signal. 21, 237–250.

During oncogenic or cellular stress new genes are frequently (over)-expressed that could be exploited for targeted cancer therapy. The enzyme, NAD(P)H:quinone oxidoreductase-1 (NQO1) is over-expressed in most solid cancers, including 60% of primary and metastatic breast cancers regardless of subtype. Normally, NQO1 detoxifies quinones resulting in the formation of stable hydroquinones that are subsequently excreted from the cell. However, NQO1 bioreduction can turn certain rare quinones, such as β-lapachone and deoxynyboquinone (DNQ), into potent cell death-inducing compounds. These agents cause severe DNA damage, poly(ADP-ribose)polymerase-1 (PARP1) hyperactivation, NAD+/ATP loss, and programmed necrosis of NQO1-expressing cancer cells. Although ß-lapachone (ARQ761) is in current clinical trials at UTSW, more potent tumor-selective NQO1 compounds are needed. Based on its structure and mode of action, isobutyl-DNQ (IB-DNQ) was recently added to the spectrum of NQO1 substrates as a more selective and potent anti-cancer agent whose mechanism of action remains to be elucidated. Although NQO1 expression is a major determinant of IB-DNQ-induced lethality, previously published results from our group showed that increased catalase expression could cause marked cytoprotection. We conducted a screen for NQO1:Catalase ratios in 266 breast tumor samples, and 143 normal breast samples, for a total of 409 specimens. We found that NQO1 expression was significantly elevated in breast tumors compared to normal tissue. In contrast, catalase expression was suppressed in breast tumors versus adjacent normal tissue. These results predict that normal tissue, which typically has higher catalase levels than cancer cells, could be selectively spared from IB-DNQ-induced toxicity. Thus, NQO1:Catalase ratios favor use of IB-DNQ in breast cancers to exploit this large therapeutic window. Since NQO1 bioactivatable drugs synergize with agents that damage DNA, we hypothesized that certain cancer vulnerabilities (e.g., BRCA1-deficient breast cancers) that have elevated endogenous DNA damage would synergize with IB-DNQ. Exposure of breast cancer cells with IB-DNQ induced DNA damage, PARP1 hyperactivation, dramatic loss of essential nucleotides (NAD+/ATP), and µ-calpain-mediated programmed necrosis with 10X greater potency than ß-lapachone. IB-DNQ-induced DNA double-strand breaks (DSBs) that occurred in cells in S/G2 phases were mainly repaired by error-free homologous recombination (HR), and therefore BRCA1-deficient cancers, being HR defective, would be particularly vulnerable to IB-DNQ treatment. Indeed, HCC1937 breast cancer cells, deficient in BRCA1, were extremely sensitive to low dose IB-DNQ due to the overwhelming levels of IB-DNQ-induced DNA damage and their inability to repair it due to their compromised HR. In fact, IB-DNQ was far superior to PARP inhibitors in targeting BRCA1-deficient cells. Studies in vivo showed equivalent antitumor efficacy of IB-DNQ to β-lapachone and DNQ, but with much greater potency at lower doses. These findings offer preclinical ‘proof-of-concept’ for IB-DNQ as a potent chemotherapeutic agent for the treatment of breast cancers, especially those deficient in BRCA1. This research was supported by grant CA102972 to DAB. Citation Format: Mariya Ilcheva, Lifen Cao, Sandeep Burma, David Boothman. Exploiting Isobutyl-deoxynyboquinone-induced DNA damage responses and metabolic changes for breast cancer therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-02.

Graphene–TiO2 multilayer films were prepared using plasma enhanced chemical vapor deposition (PECVD) and magnetron sputtering. Inserting graphene into TiO2 induced significant enhancement of the TiO2 Raman signal, which was mainly based on the charge transfer between TiO2 and graphene. The insertion of graphene also greatly affected the surface morphology of the TiO2 films, leading to increased specific surface area. The adsorption capacity and UV photocatalytic activity of the samples were investigated in the process of methyl orange (MO) decomposition and it was found that graphene–TiO2 multilayer films exhibited improved photodegradation efficiency compared to pure TiO2 films.

Pancreatic cancer will be the second leading cause of cancer-related deaths in the US by 2020, where 5-year survival is To improve its efficacy, we examined the synergistic effects of adding the AP site-modifying drug and base excision repair (BER) inhibitor, methoxyamine (MeOX), with beta-lap against NQO1 over-expressing pancreatic cancer cells. MeOX + beta-lap synergy resulted in: a, enhanced lethality of sublethal doses of beta-lap, reducing the shoulder (Dq), increasing the lethality rate (Do), and inducing apoptosis (TUNEL+) in NQO1+, but not in NQO1-, MIA PaCa-2 cells; b, increased DNA lesion formation; c, dramatic losses in ATP levels, with little recovery; and d, dramatic suppression of glycolysis. These data strongly suggests that MeOX enhances PARP1 hyperactivation and synergistic cell killing of beta-lap. Similar results were noted in shRNA-XRCC1 knockdown cells. Mechanistically, our data suggests that PARP1 detects MeOX-AP modified sites or SSBs, allowing PARP1 hyperactivation and synergistic cell death. Since MeOX is a nontoxic agent, and both agents are currently in clinical trials (i.e., beta-lap as Arq761, Arqule, Boston, MA), combination therapies for the treatment of pancreatic, as well as other NQO1 over-expressing solid cancers could be rapidly developed. An AACR Innovator Award from the George and June Block Foundation to DAB supported this work. Citation Format: Xiuquan Luo, Longshan Li, Xiumei Huang, Lifen Cao, Zachary Moore, Ralph Deberardinis, Rolf Brekken, Stanton Gerson, Lili Liu, David A. Boothman. Inhibiting base excision repair synergistically enhances beta-lapachone-mediated ‘kiss of death’ for tumor-selective therapy of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3344. doi:10.1158/1538-7445.AM2013-3344