Systematic Meta-Analysis of Computer-Aided Detection of Breast Cancer Using Hyperspectral Imaging

Computer-aided breast cancer detection and classification in mammography: A comprehensive review

Background: Our team has shown that younger versus older women, and both Blacks and Hispanics breast cancer (BC) survivors versus White women have a higher mortality after a second cancer. We have also shown that county-level neighborhood poverty is associated with increased cancer mortality after a BC diagnosis. In this study, we assess to what extent neighborhood-level socioeconomic status (SES) contributes to high BC mortality after second cancers and compare the association to BC mortality after a first cancer. We hypothesize that social determinants are critical to address in women who develop a second cancer despite now being part of the health system. Methods: Women diagnosed with a first BC and/or second cancer after first BC between 2007 and 2019 were identified from the Maryland (MD) Cancer Registry. Census tract-level neighborhood SES environments for poverty and median income were determined using local spatial autocorrelation analysis with Local Moran’s I of MD’s five-year census-tract estimates from the American Community Survey. MD census tract estimates above or below the state mean were identified as high (H)- or low (L)- tracts, respectively. We defined four neighborhood environments for each SES indicator as H-tracts among H-tracts (HH-tracts); L-tracts among L-tracts (LL-tracts); H-tracts among LL-tracts (HL-tracts); L-tracts among HH-tracts (LH-tracts). Women at least 20 years of age diagnosed with a local or regional primary BC, received surgery, and survived more than 365 days were assigned a tract-level neighborhood SES environment for each SES indicator associated with their first and second BC diagnosis. Time-to-event analyses were used to compare BC deaths across each tract-level SES indicator neighborhood environment separately. The data was analyzed using Multivariate Cox proportional hazard regression models adjusted for age at diagnosis, tract median income, cancer stage, treatment, and Estrogen Receptor status. Models were also stratified by race/ethnicity (Non-Hispanic White, Non-Hispanic Black), age at diagnosis (<50, 50-69, =>70), and treatment (hormone therapy and chemotherapy). Results: The analytical population included 15,149 MD women diagnosed with early-stage BC, of which 2,436 developed a second cancer, and BC deaths after first BC and second cancer diagnosis was 2039 and 315, respectively. We detected a 66% (HR=1.66, 95%CI=1.09, 2.53), 14% (HR=1.14, 95%CI=0.66,1.97), and 15% (HR=1.15, 95%CI=0.73,1.81) increase in BC death for women in LL, LH, and HL median income census tracts when compared to HH median income census tracts in the neighborhood income model after second cancer diagnosis. A 30% (HR=1.30, 95%CI=0.89, 1.90), 31% (HR=1.31, 95%CI=0.90, 1.93), and 20% (HR=1.20 95%CI=0.80, 1.79) increase in BC deaths for women in HH, LH, and HL poverty census tracts when compared to LL poverty census tracts was observed in the neighborhood poverty model after second cancer diagnosis. Notably, we observed increased BC death for women in LL, LH, and HL income neighborhood environments as well as in HH and HL poverty neighborhood environments at first BC diagnosis though not as robust as the second cancer neighborhood environment observations. Finally, neighborhood-level SES environments at first BC diagnosis were not statistically associated with BC death upon second diagnosis. Conclusion: Overall, our findings highlight the importance of neighborhood-level SES, such as poverty and median income, at the time of second cancer diagnosis as a strong indicator of BC mortality after second cancer, possibly even more than after a first BC. These findings provide initial evidence of the need for continued surveillance of neighborhood-level SES factors after a first BC diagnosis, and early interventions to improve survival among this group of high-risk women. Citation Format: Ifeoma Nwigwe, Michael Desjardins, Kala Visvanathan. The impact of neighborhood-level social determinants on breast cancer mortality after a second primary breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-04-03.

In Asian countries, breast densities and the proportion of younger women with breast cancer are higher than those in Western countries. This study was designed to determine differences in stage at diagnosis of breast cancer among Korean women according to screening history. The study population was derived from the Korea National Cancer Screening Program (KNCSP). The study cohort comprised 17,689 women who were newly diagnosed with breast cancer in 2011 and were invited to undergo breast cancer screening via the KNCSP between 2002 and 2011. Ductal carcinoma in situ (DCIS) and localized breast cancer were most frequent in both ever-screened and never-screened patients. Late stage cancer was significantly more frequent in never-screened patients, compared with ever-screened patients. Compared to never-screened women, the odds ratio (OR) for being diagnosed with early stage breast cancer among screened women was 1.41 (95% Confidence Interval [CI] = 1.28–1.55). The OR for being diagnosed with early stage breast cancer was highest among patients who underwent screening three times or more (aOR = 1.89, 95% CI = 1.57–2.29). Screening by mammography was associated with diagnosis of early stage breast cancer in Korean women. However, significant increases in the diagnosis of DCIS and localized breast cancers among ever-screened patients suggest the possibility of overdiagnosis due to screening.

The association between cardiovascular disease and breast and gynecologic cancers among black female patients

BACKGROUND: Germline mutations in PALB2, BRCA2 and STK11 are well established as increasing risk of both breast and pancreatic cancer. More recently, ATM and BRCA1 mutations have also been associated with risk, but literature is limited. We investigated the prevalence of pathogenic mutations and likely pathogenic variants (“mutations”) in BRCA1/2, PALB2, STK11 and ATM, comparing mutation occurrence in individuals with diagnoses of breast cancer alone to those with both breast and pancreatic cancer primaries. Prevalence of CDKN2A (p16) mutations was also evaluated in the breast–pancreatic cohort because of its contribution to hereditary pancreatic cancer. METHODS: Clinical histories and test results were reviewed for patients undergoing multi-gene panel testing at one clinical laboratory between April 2012 and June 2015. The study population was limited to women with breast cancer only (n=27,573) and women with both breast and pancreatic cancer (n=97) without other primaries. Patients underwent comprehensive analysis of 5-49 genes, depending on the panel ordered. Demographic and clinical information was provided by clinicians on test requisition forms and pedigrees/clinic notes if provided. Gene-specific mutation frequencies were compared between women with breast cancer only and women with breast and pancreatic cancer using Fisher's exact test. RESULTS: Mutations were identified in BRCA1, BRCA2, PALB2 or ATM in 13 of the 97 breast - pancreatic cancer probands (13.4%) and 1,255 of the 27,573 breast cancer probands (4.6%). Gene-specific mutation frequencies and statistical comparisons may be found in Table 1. ATM mutations were significantly more likely to be identified in women with breast and pancreatic cancer compared to breast cancer alone (Table 1). Interestingly, no CDKN2A or STK11 mutations were identified in the breast plus pancreatic cohort, although this may have been limited by the small number of individuals tested for this gene. Of those 13 women with breast and pancreatic cancers who had identified mutations, 11 (85%) had diagnoses of breast cancer over age 50. Table 1. Mutation FrequenciesGeneMutation Frequence n/N (%)Mutation Frequence n/N (%)pOR (95% PI) Breast & PancreaticBreast Only ATM6/89 (6.74%)209/17,570 (1.19%)0.000766.00(2.12,13.85)BRCA12/90 (2.22 %)429/26,336 (1.63%)0.661.37(0.16,5.14)BRCA24/90 (4.44%)442/26,336 (1.68%)0.0662.72 (0.72,7.28)CDKN2A0/54 (0.00%)13/3,965 (0.33%)10.00 (0, 24.70)PALB21/891.12% 175/17,570 (1%)0.591.13(0.03, 6.54)STK110/860.00% 0/16,931 (0.00)1Inf (0, Inf) CONCLUSION: This exploratory study substantiates the association of deleterious germline ATM mutations with predisposition to both breast and pancreatic cancers. These results also suggest that mutations in ATM may account for a larger portion of inherited breast and pancreatic cancer kindreds than mutations in other well-described genes such as BRCA2, PALB2 and STK11. A personal history of breast and pancreatic cancer may warrant the expansion of current NCCN testing criteria as a single indicator for germline testing, and that pancreatic screening consortia (CAPS) consider inclusion of ATM mutations in screening recommendations. Citation Format: Gordon OK, Childers K, McFarland R, Laduca H. ATM mutations contribution to hereditary breast-pancreatic cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-07.

ความเป็นมา การตอบสนองทางพยาธิวิทยาภายหลังการได้รับยาเคมีบำบัดก่อนผ่าตัดมีความสัมพันธ์กับผลลัพธ์ทางคลินิก ปัจจุบันไม่มีปัจจัยใดที่สามารถทำนายการตอบสนองต่อยาเคมีบำบัดในมะเร็งเต้านมชนิดมีตัวรับฮอร์โมนและไม่มีตัวรับเฮอร์ทูได้อย่างแม่นยำ เช่นเดียวกับ Ki-67 การแสดงออกของโปรตีน MCM2 ซึ่งมีหน้าที่ควบคุมการสังเคราะห์ดีเอ็นเอในระดับสูงบ่งชี้ถึงการแบ่งตัวของเซลล์ที่รวดเร็ว และมีความสัมพันธ์กับการพยากรณ์โรคที่ไม่ดีในมะเร็งหลายชนิดรวมถึงมะเร็งเต้านม การศึกษานี้มีวัตถุประสงค์เพื่อศึกษาการแสดงออกของ MCM2 ในชิ้นเนื้อก่อนได้รับยาเคมีบำบัดเพื่อทำนายการตอบสนองทางพยาธิวิทยาแบบ RCB 0/I ในมะเร็งเต้านมระยะต้นชนิดมีตัวรับฮอร์โมนและไม่มีตัวรับเฮอร์ทู วิธีการศึกษา ทบทวนเวชระเบียนอิเล็กทรอนิกส์ของผู้ป่วยมะเร็งเต้านมระยะต้นชนิดมีตัวรับฮอร์โมนและไม่มีตัวรับเฮอร์ทูที่ได้รับยาเคมีบำบัดก่อนผ่าตัดในโรงพยาบาลจุฬาลงกรณ์ ระหว่าง 1 มกราคม 2558 - 31 ธันวาคม 2563 นำชิ้นเนื้อก่อนได้รับยาเคมีบำบัดตรวจการแสดงออกของ MCM2 ด้วยการย้อมอิมมูโนฮิสโตเคมีและทบทวนลักณะทางพยาธิวิทยาเพื่อคำนวน RCB index ในชิ้นเนื้อหลังได้รับยาเคมีบำบัด คำนวนการติดสีของ MCM2 ด้วยโปรแกรมวิเคราะห์ภาพ Aperio Imagescope ผลการวิจัย ผู้ป่วยทั้งหมด 88 คน มีค่ามัธยฐานอายุ 49 ปี (พิสัย 27-80 ปี) 61.4% เป็นวัยก่อนหมดประจำเดือน มีระยะโรคมะเร็งทางคลินิก cT4 และ cN1 40% และ 66.7% ตามลำดับ เป็นมะเร็งเต้านมชนิด invasive ductal carcinoma 91.1% มีระดับทางพยาธิวิทยาระดับที่ 2 58.9% มีการแสดงออกของ ER >10% 92.2% และสถานะ PR เป็นลบ 22.2% ในชิ้นเนื้อมะเร็งเต้านมทั้งหมด 72 ชิ้นที่สามารถย้อม MCM2 และประเมิน RCB index ได้ พบว่าการแสดงออกของ MCM2 >=40% มีความสัมพันธ์กับการตอบสนองทางพยาธิวิทยาแบบ RCB 0/I อย่างมีนัยสำคัญทางสถิติจากการวิเคราะห์แบบ univariate analysis (OR = 18.33 ช่วงความเชื่อมั่น 95% = 1.88-178.98 p-value = 0.012) ปัจจัยทางพยาธิวิทยาคลินิกที่พบว่ามีความสัมพันธ์กับ MCM2 >=40% คือ ระดับของพยาธิวิทยาระดับที่ 3 การแสดงออกของ ER <=10% สถานะ PR เป็นลบ และ Ki-67 >=20% แต่ในการวิเคราะห์แบบ multivariate analysis ไม่มีปัจจัยทางพยาธิวิทยาคลินิกใดสัมพันธ์กับการตอบสนองทางพยาธิวิทยาแบบ RCB 0/I ลักษณะทางอิมมูโนฮิสโตเคมีก่อนและหลังให้ยาเคมีบำบัดมีลักษณะโดยรวมใกล้เคียงกัน ค่ามัธยฐานของการปลอดโรค และอัตราการปลอดโรคที่ 3 ปี ไม่มีความแตกต่างกันอย่างมีนัยสำคัญทางสถิติระหว่างผู้ป่วยที่มีการตอบสนองทางพยาธิวิทยาแบบ RCB 0/I และ RCB II/III สรุปผลการวิจัย การแสดงออกของ MCM2 >=40% ด้วยการตรวจทางอิมมูโนฮิสโตเคมี ในชิ้นเนื้อก่อนได้รับยาเคมีบำบัดของผู้ป่วยมะเร็งเต้านมระยะต้นชนิดมีตัวรับฮอร์โมนและไม่มีตัวรับเฮอร์ทู มีความสัมพันธ์กับการตอบสนองแบบ RCB 0/I การตรวจการแสดงออกของ MCM2 อาจช่วยทำนายประโยชน์ของยาเคมีบำบัดก่อนผ่าตัดในผู้ป่วยกลุ่มนี้ได้ อย่างไรก็ตามควรมีการศึกษาเพิ่มเติมในประชากรที่มีขนาดใหญ่ขึ้นเพื่อยืนยันผลของการศึกษานี้

A time for creative collaboration

Breast cancer (BC) and genital organ cancers (GOC) are known to have a major impact on the quality of life of patients. The aim of this study was to analyze the risk of depression, anxiety, and adjustment disorders in women in Germany with a suspected but unconfirmed diagnosis of BC or GOC in their medical history. This study included women who received a suspected diagnosis of BC or GOC and were followed between 2007 and 2015 (index date). These women were matched (1:1:1) by age to women with a confirmed diagnosis of BC or GOC and women without a cancer diagnosis. The main outcome measure of the study was the rate of depression, anxiety, and adjustment disorder diagnoses within 3years of the index date. The present analysis included a total of 4,842 patients (mean age=49.3years). Within 3years of the index date, 23.5% of women with a confirmed diagnosis of BC or GOC, 14.1% of those with a suspected diagnosis of BC or GOC, and 10.5% of those without a cancer diagnosis developed depression, anxiety, or an adjustment disorder (log-rank p value <0.001). Women with a suspected diagnosis of cancer were at a higher risk for these psychiatric conditions than those without a cancer diagnosis (BC and GOC: HR 1.32; BC: HR 1.21; GOC: HR 1.50). A suspected diagnosis of BC or GOC in a woman's medical history is associated with an increased risk of developing depression, anxiety, and adjustment disorders.

Background: The role of HER2 expression in HER2 negative breast cancer is evolving. Whether HER2 expression has an impact on ER positive, HER2 negative early-stage breast cancer in unclear. Oncotype DX assay Recurrence Score comprises of standardized quantitative HER2 mRNA expression levels by RT-PCR. The objective of this study was to investigate the impact of Oncotype HER2 score on tumor characteristics and outcome. Methods: All women assigned to the Clalit Health Services registry between 2006 to 2011 with ER positive, HER2 negative early-stage breast cancer whose tumor were sent for oncotype were identified. Patients in which HER2 score was reported in the oncotype results were included. Differences in age, tumor characteristics and chemotherapy administration between lower HER2 score (H1), i.e. HER2 score ≤ 9.1, to higher HER2 score (H2), i.e. 9.2-10.7, were analyzed. 5-year Kaplan–Meier for distant recurrence free survival (DRFS) and overall survival (OS) were estimated and differences between H1 and H2 were evaluated. Analyses were repeated separately for node negative and for node positive (N mic and 1-3 lymph nodes) disease. Results: A total of 1535 patients were included, 948 patients with node negative disease and 587 with node positive disease. Of these, 814 and 721 patients were categorized to the H1 and H2 groups, respectively. Median follow-up was 5.4 years. The distribution of oncotype RS was different, with significantly lower proportion of patients with RS between 0-10 and higher proportion of RS above 25 in the H1 group compared to the H2 groups. This difference was identified both for patients with node negative and node positive disease (Table). The distributions of age, tumor size and histological subtype were comparable between the H1 and the H2 groups, both for node negative and node positive disease. Within each RS group, administration of chemotherapy was comparable between H1 and H2 groups, regardless of nodal involvement. DRFS and OS were not associated with HER2 score. For RS 0-25, node negative disease, 5-year DRFS was 96.2% in H1 and 96.4% in H2 groups (p=0.92) and 5-year OS was 97.2% in H1 and 98.1% in H2 groups (p=0.39). For RS &amp;gt;25, node negative disease, 5-years DRFS was 89% in H1 and 90.8% in H2 groups (p=0.33) and 5-year OS was 90.6% in H1 and 90.8% in H2 groups (p=0.7). Similarly, for node positive disease, DRFS and OS were comparable between H1 and H2 group in all subgroups. Conclusions: Low HER2 mRNA expression by Oncotype RT-PCR assay was associated with significantly high Oncotype RS. Patients' outcome was not directly affected by HER2 score and was determined by RS. Further study is desired to clarify the role of HER2 expression in early stage, luminal breast cancer. Table. Comparison of age and tumor characteristics between low (H1) and high (H2) HER2 score Citation Format: Hadar Goldvaser, Raz Mutai, Salomon Stemmer, Iryna Kuchuk, Margarita Tokar, Shani Paluch-Shimon, Rinat Yerushalmi, Karen Drumea, Ella Evron, Amir Sonnenblick, Einav Gal-Yam, Gil Bar Sela, Ayelet Shai, Rotem Merose, Avital Bareket-Samish, Lior Soussan-Gutman. The impact of Human Epidermal growth factor Receptor 2 (HER2) expression by RT-PCR on tumor characteristics and outcome in estrogen receptor (ER) positive, HER2 negative early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-08.

eP061: Genetic risk for breast and ovarian cancer in a diverse and unselected population

disease control. Palbociclib plus fulvestrant allowed patients to maintain good quality of live (QoL) in the endocrine resistance setting while experiencing substantially delayed disease progression [5]. In the phase II trial PALOMA 1 evaluating palbociclib in combination with letrozole in treatment-naive patients, an improvement in progression-free survival could be seen (26.1 vs. 7.5 months) [6]. The results of the phase III trial PALOMA 2 evaluating letrozole with or without palbociclib in HR-positive, HER2negative advanced breast cancer patients presented at the ASCO Annual Meeting in June 2016 confirmed these positive findings [7]. All trials illustrate the high potential of CDK4/6 inhibition and the clinical impact of this new treatment approach. In this issue of Breast Care, Marcus Schmidt will highlight pre-clinical data and early clinical trials which led to an accelerated approval of palbociclib by the US Food and Drug Administration (FDA) as first-line treatment in combination with letrozole in advanced HR-positive and HER2-negative breast cancer [8]. Johannes Ettl adds more data about the clinical trials investigating palbociclib [9]. To date, 2 large clinical trials have been fully published and one was presented at a meeting. In his article, he discusses the results of these trials and their clinical relevance for the management of HR-positive advanced breast cancer. In addition, he gives information about QoL measurement in patients treated in the PALOMA 3 trial. Romualdo Barroso-Sousa and colleagues give an overview about new upcoming components, mainly abemaciclib and ribociclib [10]. The preclinical and clinical data are described as well as toxicity profiles and drug action. Ribociclib has already been investigated in the combination with antiestrogens in the MONALEESA trials and also with additional PI3K inhibitors. Abemaciclib is the only CDK4/6 inhibitor that passes the blood-brain barrier. But it also has a different toxicity profile. The combination with antiestrogens has been investigated in the MONARCH trials. Selective CDK4/6 inhibitors represent an important therapeutic advance in HR-positive breast cancer. The role in other breast canAlmost two thirds of breast cancers express the estrogen receptor (ER), which plays an important role in malignant growth stimulation and as therapeutic target. In postmenopausal patients, aromatase inhibitors (AI, e.g., letrozole and anastrozole) have become the treatment of choice in first-line therapy [1]. Unfortunately, some patients have a primary or de novo resistance to first-line endocrine therapy and even patients who initially respond will acquire resistance to treatment and relapse. On disease progression, second-line treatment options include other classes of AI (steroidal or nonsteroidal) and the ER antagonists fulvestrant and tamoxifen [2]. The study of resistance to endocrine therapies in hormone receptor (HR)-positive breast cancer has aimed at identifying new therapeutic strategies that enhance the efficacy of endocrine therapies. However, endocrine resistance is a frequent problem in breast cancer treatment. Yet, insights into estrogen mediated signaling allowed the development of therapeutic approaches interacting with the cell cycle which might overcome endocrine resistance in breast cancer patients. Dysregulation of the cell-cycle control is a frequent event in breast cancer and occurs via a number of different mechanisms. These dysregulations involving components of CDK4/6 and cyclin D lead to a survival advantage of the cancer cell. CDK4/6 inhibition can reduce cell growth and suppress DNA replication in tumors with functional tumor-suppressor retinoblastoma protein (RB). The cell-cycle machinery is important for efficacy of hormonal therapy in breast cancer, as ER-positive RB-negative xenograft models are resistant to tamoxifen [3]. In ER-positive metastatic breast cancer, often several lines of therapy are effective until patients require chemotherapy. Cellcycle control is a very promising additional option to prolong progression-free survival and time until chemotherapy is needed. Results from the phase III study PALOMA 3 showed that adding palbociclib to fulvestrant more than doubled the duration of disease control. Women with previously treated, HR-positive, HER2negative advanced breast cancer [4] gained almost 5 months of Published online: June 22, 2016

BackgroundCardiovascular disease (CVD) is the leading cause of morbidity and mortality among older postmenopausal women. The impact of postmenopausal breast cancer on CVD for older women is uncertain. We hypothesized that older postmenopausal women with breast cancer would be at a higher risk of CVD than similar aged women without breast cancer and that CVD would be a major contributor to the subsequent morbidity and mortality.MethodsIn a prospective Women’s Health Initiative study, incident CVD events and total and cause-specific death rates were compared between postmenopausal women with (n = 4,340) and without (n = 97,576) incident invasive breast cancer over 10 years post-diagnosis, stratified by 3 age groups (50–59, 60–69, and 70–79).ResultsPostmenopausal women, regardless of breast cancer diagnosis, had similar and high levels of CVD risk factors (e.g., smoking and hypertension) at baseline prior to breast cancer, which were strong predictors of CVD and total mortality over time. CVD affected mostly women age 70–79 with localized breast cancer (79% of breast cancer cases in 70–79 age group): only 17% died from breast cancer and CVD was the leading cause of death (22%) over the average 10 years follow up. Compared to age-matched women without breast cancer, women age 70–79 at diagnosis of localized breast cancer had a similar multivariate-adjusted hazard ratio (HR) of 1.01 (95% confidence interval [CI]: 0.76–1.33) for coronary heart disease, a lower risk of composite CVD (HR = 0.84, 95% CI: 0.70–1.00), and a higher risk of total mortality (HR = 1.20, 95% CI: 1.04–1.39).ConclusionCVD was a major contributor to mortality in women with localized breast cancer at age 70–79. Further studies are needed to evaluate both screening and treatment of localized breast cancer tailored to the specific health issues of older women.

e13114 Background: The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Irinotecan is a semi-synthetic water-soluble camptothecin derivative which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of irinotecan combined with anlotinib in second-line and above treatment of HER-2 negative advanced breast cancer. (ChiCTR2000037448) Methods: This open-label, single-arm, phase II study enrolled women aged 18 years and older with HER2-negative breast cancer who underwent ≥1 line chemotherapy, All patients were treated with irinotecan (60mg/m2, administered intravenously on Days 1 and 8 of each 21 day cycle) and anlotinib (12mg, qd, administered orally on Days 1-14 of each 21 day cycle). The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety. Results: From November 2020 to November 2022, 14 patients were enrolled in this study. Median follow-up was 10.8 months (95% CI 4.3-17.3). Median PFS was 5.9 months (95% CI 2.0-9.8). Of all the patients whose efficacy could be evaluated (13/14), no patient achieved complete response (CR); 3(23.07%) and 8(61.54%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 23.1% (95% CI 5.0-53.8) and DCR was 84.6% (95% CI 54.6-98.1). OS has not reached. The major treatment-related adverse events (incidence≥10%) were fatigue (42.86%), hypertension (42.86%), neutropenia (28.57%), hand foot syndrome (21.43%) and myelosuppression (14.29%). There is no grade 3/4 adverse events occurred.28.57% (4/14) of patients had dose reductions. Conclusions: The combination of irinotecan and anlotinib showed better treatment response and tolerable toxicity in the treatment of second-line and above patients with HER2-negative metastatic breast cancer. Further studies enrolling more patients are still needed. Clinical trial information: ChiCTR2000037448 .

12049 Background: Over the last few decades, improvements in healthcare have increased life expectancy by nearly 10 years resulting in a rise in America’s older population. As age is one of the most significant risk factors for the development of cancer, there is a projected increase in the incidence of cancer in the elderly population, with the largest absolute and relative increases in breast cancer (BC). Although treatment advances have improved outcomes for patients with metastatic breast cancer (MBC), patients in clinical trials are often younger and there is limited data for the older population. The goals of this study were to use the National Cancer Database (NCDB) to assess overall survival (OS) in older patients over 75 years of age with MBC and evaluate the impact of tumor features and demographic factors. Methods: Women with a diagnosis of BC at age ≥75 years and with metastases at time of initial diagnosis from 2010 to 2019 were identified from the NCDB. Patients were stratified into age subgroups of 75-79, 80-84, and ≥85 years. Chi-square tests were used to compare categorical variables. Kaplan Meier curves were used to determine OS distributions for patients by age, BC subtype and year of diagnosis. Log-rank tests and multivariable cox proportional hazards modeling was performed to assess the difference in OS by BC subtype. Results: Of 17,325 eligible women included in the final analysis, 39.4% were 75-79, 30.1% 80-84, and 30.4% ≥85 years of age. We observed an improvement in OS over time, with 5-year OS rates improving from 13.7% in 2010 to 15.2% in 2015, p = 0.017. Three-year OS rates were higher in patients aged 75-79 (34.2%) compared with patients aged 80-84 (28.7%) and ≥85 years (18.6%), p &lt; 0.001. Outcomes varied by BC subtype with better prognosis in patients with hormone receptor (HR)+, HER2-negative BC (3-year OS 35.1%), followed by HR+, HER2+ (32.8%), HER2+, HR-negative (20.6%) and lastly, HR-negative, HER2-negative BC (9.7%), p &lt; 0.001. Based on multivariable analyses, a higher comorbidity index was associated with worse outcomes (HR 1.654 [1.48-1.849], p &lt; 0.0001). Higher income (≥$63,000) was associated with decreased mortality (HR 0.859 [0.784-0.941], p = 0.0011) compared with lower income ( &lt; $38,000). While the type of cancer facility (academic, community, etc) did not impact mortality, older patients living in metropolitan areas ( &gt; 1 million) had improved outcomes (HR 0.829 [0.689-0.996], p = 0.046), compared to those in rural areas. Conclusions: We observed a modest though significant improvement in survival outcomes over time in older patients with MBC. Prognosis was better in patients with HR+ BC compared with HR-negative, HER2+, and HR-negative, HER2-negative subtypes. However, outcomes in patients ≥85 years remain poor. Given the lack of clinical trial data in older patients with cancer, future studies should specifically focus on improving outcomes in this population.

Breast cancer is a common and fatal disease among women worldwide. Therefore, the early and precise diagnosis of breast cancer plays a pivotal role to improve the prognosis of patients with this disease. Several studies have developed automated techniques using different medical imaging modalities to predict breast cancer development. However, few review studies are available to recapitulate the existing literature on breast cancer classification. These studies provide an overview of the classification, segmentation, or grading of many cancer types, including breast cancer, by using traditional machine learning approaches through hand-engineered features. This review focuses on breast cancer classification by using medical imaging multimodalities through state-of-the-art artificial deep neural network approaches. It is anticipated to maximize the procedural decision analysis in five aspects, such as types of imaging modalities, datasets and their categories, pre-processing techniques, types of deep neural network, and performance metrics used for breast cancer classification. Forty-nine journal and conference publications from eight academic repositories were methodically selected and carefully reviewed from the perspective of the five aforementioned aspects. In addition, this study provided quantitative, qualitative, and critical analyses of the five aspects. This review showed that mammograms and histopathologic images were mostly used to classify breast cancer. Moreover, about 55% of the selected studies used public datasets, and the remaining used exclusive datasets. Several studies employed augmentation, scaling, and image normalization pre-processing techniques to minimize inconsistencies in breast cancer images. Several types of shallow and deep neural network architecture were employed to classify breast cancer using images. The convolutional neural network was utilized frequently to construct an effective breast cancer classification model. Some of the selected studies employed a pre-trained network or developed new deep neural networks to classify breast cancer. Most of the selected studies used accuracy and area-under-the-curve metrics followed by sensitivity, precision, and F-measure metrics to evaluate the performance of the developed breast cancer classification models. Finally, this review presented 10 open research challenges for future scholars who are interested to develop breast cancer classification models through various imaging modalities. This review could serve as a valuable resource for beginners on medical image classification and for advanced scientists focusing on deep learning-based breast cancer classification through different medical imaging modalities.