Improved Breast Cancer Survival Research Articles

Conditional survival in breast cancer up to 10 years in the Nordic countries.

Survival in breast cancer (BC) has developed favorably but late recurrences are still a problem. We model survival data from the NORDCAN database and analyze 1-, 5-, and 10-year relative survival and 5/1- and 10/5-year conditional survival in BC from Denmark (DK), Finland (FI), Norway (NO), and Sweden (SE) between 1971 and 2020. Conditional survival measures survival in those who had survived year 1 to reach year 5 (5/1), or in those who had survived year 5 to reach year 10 (10/5). Almost all survival metrics were best for SE but survival in all countries improved in the course of time approaching the SE levels which were 98.3% for 1-year, 92.3% for 5-year, and 87.8% for 10-year survival. Conditional 10/5-year survival, covering 5 years, was better than 5/1-year survival, covering 4 years. A contributing factor is most likely the high rate of recurrence in period 2-5 years. The difference was observed for all countries but for DK 10/5-year survival approached 1-year survival and for NO and SE 10/5-year survival was only barely better than 5/1-year survival. The explanation to this was the excellent 10/5-year survival in DK compared to SE and particularly to NO. Literature search suggested that the reason for the relatively low 10/5-year survival in NO might be stagnant survival development in old patients. We assume that late mortality is critically limiting survival in BC and either interference with the late metastatic process or effective treatment will be key to future improvements in BC survival.

Evaluation of an Artificial Intelligence System for Detection of Invasive Lobular Carcinoma on Digital Mammography.

Introduction Early breast cancer detection with screening mammography has been shown to reduce mortality and improve breast cancer survival. This study aims to evaluate the ability of an artificial intelligence computer-aided detection (AI CAD) system to detect biopsy-proven invasive lobular carcinoma (ILC) on digital mammography. Methods This retrospective study reviewed mammograms of patients who were diagnosed with biopsy-proved ILC between January 1, 2017, and January 1, 2022. All mammograms were analyzed using cmAssist® (CureMetrix, San Diego, California, United States), which is an AI CAD for mammography. The AI CAD sensitivity for detecting ILC on mammography was calculated and further subdivided by lesion type, mass shape, and mass margins. To account for the within-subject correlation, generalized linear mixed models were implemented to investigate the association between age, family history, and breast density and whether the AI detected a false positive or true positive. Odds ratios, 95% confidence intervals, and p-values were also calculated. Results A total of 124 patients with 153 biopsy-proven ILC lesions were included. The AI CAD detected ILC on mammography with a sensitivity of 80%. The AI CAD had the highest sensitivity for detecting calcifications (100%), masses with irregular shape (82%), and masses with spiculated margins (86%). However, 88% of mammograms had at least one false positive mark with an average number of 3.9 false positive marks per mammogram. Conclusion The AI CAD system evaluated wassuccessful in marking the malignancy in digital mammography. However, the numerous annotations confounded the ability to determine its overall accuracy and this reduces its potential use in real-life practice.

Abstract 1900: Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609)

Abstract Background: Adjuvant radiotherapy (RT) following surgery significantly improves breast cancer survival. However, some patients, particularly minorities, develop early adverse skin reactions (EASRs) or skin toxicities that negatively impact the quality of life (QOL). We assess RT-related EASRs and QOL using clinician-reported outcomes (CROs) and patient-reported outcomes (PROs) in a large multi-racial/ethnic breast cancer population. Methods: This prospective study recruited 1,000 breast cancer patients undergoing RT through the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base between 2011 and 2013. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria for CROs and Skindex-16 (SD-16) for PROs. Results: This study included 405 non-Hispanic whites (NHW), 277 black/African Americans (AA), 241 HW, 62 Asian/Pacific Islanders (ASPI), and 15 others. About 42% and 15% of patients developed RT-induced ONS grade 3+ and 4+ skin toxicities, respectively. RT-induced EASRs differed significantly by race/ethnicity at mid-RT, 1-month, and 2-month post-RT, but not at the end of RT. Total SD-16 scores differ by race/ethnicity at pre-RT, 1-month, and 6-month post-RT, but not at the end of RT. Overall, PROs have a moderate but significant correlation with CROs at the end of RT. Conclusion: RT-induced EASRs differed significantly by race/ethnicity. There was a moderate but significant correlation between PROs and CROs. However, PROs delineated a broader spectrum in capturing the impact of RT on patients’ QOL, which highlights the importance of integrating PROs in accessing RT-induced EASRs, particularly in minorities with worse RT-induced EASRs. Trial Registration: NCT01407770 (09/02/2011) Citation Format: James J. Urbanic, Edward G. Shaw, Cristiane Takita, Jean L. Wright, Edward H. Ip, Lingyi Lu, Luis Baez-Diaz, Doris R. Brown, Jon Strasser, Kathy Baglan, Mark Palmer, Anu Thakrar, Amarinthia E. Curtis, Glenn Lesser, Jennifer J. Hu. Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1900.

Breast Cancer Risk and Breast-Cancer-Specific Mortality following Risk-Reducing Salpingo-Oophorectomy in BRCA Carriers: A Systematic Review and Meta-Analysis

Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59-1.21) or CBC risk (RR = 0.95, 95%CI: 0.65-1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18-0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68-1.17) or CBC risk (RR = 0.85, 95%CI: 0.59-1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07-1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41-0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30-0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers.

Identification of actionable targets for breast cancer intervention using a diversity outbred mouse model

HER2-targeted therapy has improved breast cancer survival, but treatment resistance and disease prevention remain major challenges. Genes that enable HER2/Neu oncogenesis are the next intervention targets. A bioinformatics discovery platform of HER2/Neu-expressing Diversity Outbred (DO) F1 Mice was established to identify cancer-enabling genes. Quantitative Trait Loci (QTL) associated with onset ages and growth rates of spontaneous mammary tumors were sought. Twenty-six genes in 3 QTL contain sequence variations unique to the genetic backgrounds that are linked to aggressive tumors and 21 genes are associated with human breast cancer survival. Concurrent identification of TSC22D3, a transcription factor, and its target gene LILRB4, a myeloid cell checkpoint receptor, suggests an immune axis for regulation, or intervention, of disease. We also investigated TIEG1 gene that impedes tumor immunity but suppresses tumor growth. Although not an actionable target, TIEG1 study revealed genetic regulation of tumor progression, forming the basis of the genetics-based discovery platform.

Breast cancer mammographic screening by different guidelines among women of different races/ethnicities

Mammographic screening is a common diagnostic tool for breast cancer among average-risk women. However, breast cancer screening guidelines differ between societies and organizations. Appropriate adherence to screening guidelines helps early diagnosis and treatment of breast cancer, which subsequently improves breast cancer survival. We used three national guidelines to define adherence recommended by US Preventive Services Task Force (USPSTF), American Cancer Society (ACS), and American College of Radiology (ACR), which included different criteria for age and frequency. (USPSTF: 50–74, biennial; ACS: 45–54, yearly, 55+ biennial; ACR: 40+, yearly) We hypothesized that adherence rates for mammographic screening may be lower among minorities (non-Hispanic black (NHB) and Hispanic/Latino) than among non-Hispanic whites (NHW) regardless of the guideline applied. We conducted a cross-sectional study using nationally representative survey data from the 2020 Health Information National Trends Survey (HINTS). Adherence to mammographic screening among NHW, NHB, and Hispanic/Latino populations were calculated. A total of 1,751 survey samples were used in the final analysis. Adherence rates of each guideline for average-risk woman in this study were as follows: USPSTF - 77.37%, ACS - 68.41%, and ACR - 57.71%. Additionally, our results demonstrated that the adherence rate was higher among NHB when compared with NHW women regardless of which guideline was applied. Multivariate logistic regression analysis indicated that both NHB ethnicity and insurance coverage exhibited strong positive associations with adherence to breast cancer screening. Our findings support other studies’ results that different racial/ethnic and socio-demographic factors can affect screening adherence. Therefore, healthcare providers should promote breast cancer screening especially among NHW/Hispanic women and women lacking insurance coverage.

Changes in geographic accessibility to mammography by state and rural-urban status, United States, 2006-2022.

Although mammography is widely available in the United States, differences in accessibility in rural and urban areas and changes over time are not well described. In this study, we estimated the number and proportion of women aged 45-84 years who had limited travel time-based geographic accessibility to mammography by urban-rural status and state in the contiguous United States in 2006 and 2022. The proportion of women aged 45-84 years with limited accessibility to mammography did not substantially change from 2006 (12.7%; representing 7.5 million women) to 2022 (12.2%; 8.2 million women). Accessibility to mammography varied by state, but in 10 states, more than 26% of the statewide female population aged 45-84 years had limited accessibility in 2022. This proportion was substantially higher in rural areas (50.6% overall; ≥50% in 28 states in 2022) than in urban areas (3.0% overall). Increasing accessibility to mammography could increase utilization of breast cancer screening and, potentially, improve breast cancer survival.

Toxicity Index, patient-reported outcomes, and persistence of breast cancer chemotherapy-associated side effects in NRG Oncology/NSABP B-30

Adjuvant chemotherapy improves breast cancer survival but is associated with bothersome short- and long-term toxicity. Factors associated with toxicity, especially subacute toxicity up to 2 years following chemotherapy, have not been fully elucidated. The NRG Oncology/NSABP B-30 clinical trial compared 3 different doxorubicin-, cyclophosphamide-, and docetaxel-based chemotherapy regimens given over 3–6 months. Patients with hormone receptor-positive breast cancer received subsequent adjuvant endocrine therapy. From baseline through 24 months, 2156 patients completed questionnaires serially. We used multivariable probabilistic index models to identify factors associated with acute (>0–12 months) and subacute (>12–24 months) difficulties with pain, cognition, vasomotor symptoms, and vaginal symptoms. For all symptom domains, presence of symptoms prior to chemotherapy initiation were associated with symptoms in the subacute period (all p < 0.001). In addition, different combinations of patient factors and breast cancer treatments were associated with increased likelihood of pain, vasomotor, and vaginal symptoms in the subacute period. Consideration of pre-treatment symptoms and patient factors, as well as treatments for breast cancer, can facilitate identification of groups of patients that may experience symptoms following completion of chemotherapy. This information may be important for treatment-decision-making when alternative regimens are equivalent in benefit.

Width of excision margins after breast conserving surgery for invasive breast cancer and distant recurrence and survival

One premise of cancer treatment is that if a tumour is cut out but tumour cells remain present or close to the edges (of the cut), the risk of cancer...

A randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): The Aspirin after Breast Cancer (ABC) Trial

360922 Background: In-vitro and in-vivo evidence suggests that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. Thus, we conducted a prospective randomized controlled trial to determine the true benefits and risks of adjuvant aspirin therapy for breast cancer survivors. Methods: The primary objective was to compare the effect of 300 mg aspirin daily versus placebo upon invasive disease-free survival (iDFS) in patients with high-risk, HER2-negative breast cancer. Secondary objectives included effects on overall survival, cardiovascular disease, toxicity, and adherence. Eligible participants included patients aged 18-70 diagnosed with a primary invasive HER2-negative breast cancer. If hormone receptor (HR)–positive, tumors needed to be node positive and diagnosed within the past 10 years. If HR negative, tumors could be node positive or T2-4N0 and diagnosed within the past 18 months. Participants were randomly selected (1:1) to aspirin 300 mg versus placebo daily for 5 years in a double-blinded fashion. Stratification factors include HR status (positive vs. negative), body mass index (&lt; or ≥ 30 kg/m2), and stage (II vs. III). Based upon an accrual goal of 2,936 patients to reach 381 iDFS events, the study was estimated to have 80% power to detect HR 0.75. Results: From January 2017 to December 2020, 3,021 participants were enrolled. Treatment arms were well balanced in terms of key characteristics. In November 2021, the Data Safety and Monitoring Board recommended that the trial be unblinded because the stratified hazard ratio had crossed a pre-specified futility boundary. After 191 iDFS events (aspirin: 107, placebo: 84) and median follow-up of 20 months, the stratified hazard ratio comparing aspirin to placebo was 1.27 (z-score: -1.64), which is greater than the pre-specified hazard ratio of futility 1.03 (z-score &lt; -0.192). There was no difference in the frequency of grade 3/4 adverse events by study arm. Compliance was high and similar across arms. Non-protocol use of aspirin/non-steroidal anti-inflammatory drugs was similar across arms and less than 14%, consistent with prior randomized aspirin trials. Updated results on iDFS events will be provided at presentation. Conclusions: In this double-blinded, placebo-controlled, randomized trial, there was no benefit in breast cancer invasive disease-free survival with the addition of 300 mg aspirin daily. Although inflammation may still play a role in cancer progression, aspirin is not recommended for prevention of breast cancer recurrence. Clinical trial information: NCT02927249.

Improvement of survival in Korean breast cancer patients over a 14-year period: A large-scale single-center study.

PurposeThe aim of this study was to evaluate the chronological changes over 14 years in the survival of Korean patients with breast cancer. We also sought to investigate the factors that may have influenced the changes in survival rate.Materials and methodsWe retrospectively analyzed 17,776 breast cancer patients who were treated at Asan Medical Center between January 2000 and December 2013. Patient information was collected from the Asan database, including age at diagnosis, clinical manifestation, pathology report, types of treatment and modality, types of recurrence, and follow-up period. We classified the patients into two cohorts according to the year of their surgery (P1: 2000–2007 and P2: 2008–2013) and compared survival and recurrence between both cohorts.ResultsWe observed that patients treated more recently had better survival outcomes. The 5-year breast cancer-specific survival increased from 94.0% in P1 to 96.6% in P2 (p<0.001), and the 5-year disease-free survival increased from 87.9% in P1 to 91.2% in P2 (p<0.001). When analyzed by type of recurrence, distant metastasis-free survival increased to a significant degree. In subgroup analysis by the subtypes of breast cancer, the survival rates improved in all of the subtypes except triple negative breast cancer, and the improvement was more prominent in subtypes with overexpressed human epidermal growth factor receptor 2.ConclusionThis study showed improvement in breast cancer survival over the succeeding years, which is consistent with the advancement in systemic therapy.

Breast cancer awareness and downstaging practices among adult women in Gulu City Main Market in Northern Uganda: A cross-sectional study

Background: Breast Cancer is one of the most common cancers that occur universally among women. The disability-adjusted life years lost by women to breast cancer globally are more than any other cancer. Breast cancer occurs in women worldwide after puberty with increasing rates in later life. Improvements in breast cancer survival began in the 1980s in countries where early detection programs combined with different modes of treatment to eradicate the invasive form of the disease are practiced. Recent data show a higher prevalence of breast cancer among women in Northern Uganda compared to the rest of the country. This study aimed to determine factors associated with breast cancer awareness, breast self-examination, clinical breast examination, and other modalities for screening and early breast cancer detection among adult women in Gulu Main Market. Methods: We conducted a cross-sectional study in Gulu's Main Market in 2020. We recruited Ninety-eight adult women for the study using a random sampling method. The questionnaire had an internal validity of Cronbach's α=0.72, and a local IRB approved the study. We used SPSS version 26.0 for data analysis, and a p-value less than 0.05 was considered significant. Results: Most participants were 20-29 years 41(41.8%), married 44(44.9%), monthly incomes of more than one million shillings 51(52.2%), Acholi 81(82.7%), Catholics 46(46.9%), vendors 75(76.5%), work duration in the Market (1-10 years) 64(65.4%), primary level of education 39(39.8%), and had 1-2 pregnancies 37(37.8%). The independent factors associated with breast cancer awareness, breast self-examination, and clinical breast examination were vendor (primary occupation) (β=-0.130, t=-2.979, p=0.004), work duration in the Main Market (1-10 years) (β=-0.186, t=-2.452, p=0.016), and the highest level of education (β=-0.091, t=-2.506, p=0.014). Conclusions: Breast cancer awareness and downstaging practices among adult women in Gulu's Main Market are thought-provoking. Women with better socioeconomic status (higher education level, moderate work duration in the Market, and vendors) in Gulu Main Market were more likely aware and practiced breast cancer downstaging activities. There is a need to strengthen publicity on breast cancer-related knowledge for lower-income occupational groups and those with lower educational levels to understand better the importance of conducting early breast cancer detection activities.

Achieving High Breast Cancer Survival for Women in Rural and Remote Areas.

Background:Significant improvements in breast cancer survival have been made in the past few decades in many developed countries including Australia with a five-year relative survival of 90%. The aim of the present study is to obtain a brief estimate of the relative importance of demographic factors such as rurality, socio-economic standard and ethnicity versus traditional risk factors for women diagnosed with breast cancer in Far North Queensland, Australia. Methods:This was a retrospective longitudinal study of all women diagnosed with their first episode of breast cancer in 1999-2013 in Far North Queensland, Australia. Cox proportional hazards regression analysis was used to identify factors independently associated with mortality for women with any type of breast cancer (in situ or invasive) and for women with invasive cancer. Life tables were used to assess five and ten-year absolute survival. Standard linear regression and binary logistic regression were used to identify any association between demographic factors and late presentation. Results:Five and ten-year absolute survival was 0.90 and 0.86 respectively. Aboriginal and Torres Strait Islander status, remoteness of area of residence, and socioeconomic status were not associated with more advanced disease at presentation or increased risk of breast cancer death. Only traditional risk factors such as increased tumour size, absence of progesterone receptor, high tumour grade and presence of metastasis in axillary lymph nodes were associated with increased risk of breast cancer death. Conclusion:The effect of the classical risk factors on breast cancer mortality outweighs the effects of demographic factors. The fact that ethnicity, remoteness and socioeconomic status is not associated with late presentation or breast cancer death suggests that given appropriate resources it may be possible to close the gap of inequalities in breast cancer.

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research.

The impact of scaling up access to treatment and imaging modalities on global disparities in breast cancer survival: a simulation-based analysis.

Female breast cancer is the most commonly diagnosed cancer in the world, with wide variations in reported survival by country. Women in low-income and middle-income countries (LMICs) in particular face several barriers to breast cancer services, including diagnostics and treatment. We aimed to estimate the potential impact of scaling up the availability of treatment and imaging modalities on breast cancer survival globally, together with improvements in quality of care. For this simulation-based analysis, we used a microsimulation model of global cancer survival, which accounts for the availability and stage-specific survival impact of specific treatment modalities (chemotherapy, radiotherapy, surgery, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single-photon emission computed tomography [SPECT]), and quality of cancer care, to simulate 5-year net survival for women with newly diagnosed breast cancer in 200 countries and territories in 2018. We calibrated the model to empirical data on 5-year net breast cancer survival in 2010-14 from CONCORD-3. We evaluated the potential impact of scaling up specific imaging and treatment modalities and quality of care to the mean level of high-income countries, individually and in combination. We ran 1000 simulations for each policy intervention and report the means and 95% uncertainty intervals (UIs) for all model outcomes. We estimate that global 5-year net survival for women diagnosed with breast cancer in 2018 was 67·9% (95% UI 62·9-73·4) overall, with an almost 25-times difference between low-income (3·5% [0·4-10·0]) and high-income (87·0% [85·6-88·4]) countries. Among individual treatment modalities, scaling up access to surgery alone was estimated to yield the largest survival gains globally (2·7% [95% UI 0·4-8·3]), and scaling up CT alone would have the largest global impact among imaging modalities (0·5% [0·0-2·0]). Scaling up a package of traditional modalities (surgery, chemotherapy, radiotherapy, ultrasound, and x-ray) could improve global 5-year net survival to 75·6% (95% UI 70·6-79·4), with survival in low-income countries improving from 3·5% (0·4-10·0) to 28·6% (4·9-60·1). Adding concurrent improvements in quality of care could further improve global 5-year net survival to 78·2% (95% UI 74·9-80·4), with a substantial impact in low-income countries, improving net survival to 55·3% (42·2-67·8). Comprehensive scale-up of access to all modalities and improvements in quality of care could improve global 5-year net survival to 82·3% (95% UI 79·3-85·0). Comprehensive scale-up of treatment and imaging modalities, and improvements in quality of care could improve global 5-year net breast cancer survival by nearly 15 percentage points. Scale-up of traditional modalities and quality-of-care improvements could achieve 70% of these total potential gains, with substantial impact in LMICs, providing a more feasible pathway to improving breast cancer survival in these settings even without the benefits of future investments in targeted therapy and advanced imaging. Harvard T H Chan School of Public Health, and National Cancer Institute P30 Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center.

Screening mammography mitigates breast cancer disparities through early detection of triple negative breast cancer

PurposeScreening mammography improves breast cancer survival through early detection, but Triple Negative Breast Cancer (TNBC) is more difficult to detect on mammography and has lower survival compared to non-TNBC, even when detected at early stages. TNBC is twice as common among African American (AA) compared to White American (WA) women, thereby contributing to the 40% higher breast cancer mortality rates observed in AA women. The role of screening mammography in addressing breast cancer disparities is therefore worthy of study. MethodsOutcomes were evaluated for TNBC patients treated in the prospectively-maintained databases of academic cancer programs in two metropolitan cities of the Northeast and Midwest, 1998–2018. ResultsOf 756 TNBC cases, 301 (39.8%) were mammographically screen-detected. 46% of 189 AA and 38.5% of 460 WA patients had screen-detected TNBC (p = 0.16). 25.3% of 257 TNBC cases ≤50 years old had screen-detected disease compared to 47.3% of 499 TNBC cases >50 years old (p < 0.0001).220/301 (73.1%) screen-detected TNBC cases were T1 lesions versus 118/359 (32.9%) non-screen-detected cases (p < 0.0001). Screen-detected TNBC was more likely to be node-negative (51.9% v. 40.4%; p < 0.0001).Five-year overall survival was better in screen-detected TNBC compared to nonscreen-detected TNBC (92.8% v. 81.5%; p < 0.0001) in the entire cohort. The magnitude of this effect was most significant among AA patients (Fig. 1). Screening-related survival patterns were similar among AA and WA patients in both cities. ConclusionData from two different cities demonstrates the value of screening mammography to mitigate breast cancer disparities in AA women through the early detection of TNBC.

Targeting PI3K/AKT/mTOR Signaling Pathway in Breast Cancer.

Simple SummaryPI3K signaling pathway plays an essential role in many cellular processes and is frequently altered in breast cancer, leading to increased tumor growth and reduced survival. Small molecule inhibitors have been developed that target the three key elements of this pathway: PI3K, AKT, and mTOR. Despite demonstrating promising preclinical activity, intrinsic and acquired resistance, as well as high levels of adverse reactions, partially limited the therapeutic efficacy of PI3K/AKT/mTOR inhibitors. To increase therapeutic benefit, drug combinations and schedules need to be explored to identify those with the highest efficacy and lowest toxicity rate. In addition, defining appropriate patient subpopulations, for either monotherapy or drug combinations, and identifying predictive biomarkers remain a challenge. Breast cancer is the most frequently diagnosed cancer and the primary cause of cancer death in women worldwide. Although early diagnosis and cancer growth inhibition has significantly improved breast cancer survival rate over the years, there is a current need to develop more effective systemic treatments to prevent metastasis. One of the most commonly altered pathways driving breast cancer cell growth, survival, and motility is the PI3K/AKT/mTOR signaling cascade. In the past 30 years, a great surge of inhibitors targeting these key players has been developed at a rapid pace, leading to effective preclinical studies for cancer therapeutics. However, the central role of PI3K/AKT/mTOR signaling varies among diverse biological processes, suggesting the need for more specific and sophisticated strategies for their use in cancer therapy. In this review, we provide a perspective on the role of the PI3K signaling pathway and the most recently developed PI3K-targeting breast cancer therapies.

Breast Cancer in Adolescent and Young Adult Women Under the Age of 40 Years.

In the United States, one in 196 women is diagnosed with breast cancer under the age of 40 years. Adolescents and young adults (AYAs), of age 15-39 years at diagnosis, experience a number of unique challenges when confronting breast cancer. The incidence of invasive breast cancer has increased among AYA women in the United States since 2004, and most of this change is due to an increase in young women diagnosed with distant disease. AYAs are more likely than older women to present with aggressive subtypes and advanced disease, and they often require systemic staging at diagnosis. Clinical trials should be considered whenever possible, particularly in AYAs with locally advanced or metastatic disease at diagnosis and those with disease progression or recurrence. A significant proportion of AYAs carry germline cancer predisposition mutations, which necessitates prompt genetic testing for all AYAs at diagnosis and may influence choice of local therapy. Suppression of ovarian function, as an adjunct to chemotherapy, may improve breast cancer survival in AYAs. To provide optimal care for AYAs with breast cancer, clinicians should engage multidisciplinary teams that offer fertility preservation, genetic counseling, physical and occupational therapy, nutrition, and psychosocial support, along with medical expertise in tailoring cancer-directed therapy and symptom management toward young women.

Tamoxifen use in microvascular breast reconstruction &amp; its effect on microvascular complications: a systematic review &amp; meta-analysis

Background: Tamoxifen is a selective oestrogen receptor modulator that is used in the treatment of hormone receptor positive breast cancer. It has been shown to significantly reduce the risk of breast cancer recurrence and has been shown to improve breast cancer survival. It is however associated with an increased risk of thromboembolic events, with an increased risk in patients undergoing free flap breast reconstruction due to the prolonged period of immobility. As tamoxifen has implications for macrovascular thrombosis, this study aimed to assess if it has implications for microvascular thrombosis.

FAK inhibition alone or in combination with adjuvant therapies reduces cancer stem cell activity

Cancer stem-like cells (CSC) contribute to therapy resistance and recurrence. Focal adhesion kinase (FAK) has a role in CSC regulation. We determined the effect of FAK inhibition on breast CSC activity alone and in combination with adjuvant therapies. FAK inhibition reduced CSC activity and self-renewal across all molecular subtypes in primary human breast cancer samples. Combined FAK and paclitaxel reduced self-renewal in triple negative cell lines. An invasive breast cancer cohort confirmed high FAK expression correlated with increased risk of recurrence and reduced survival. Co-expression of FAK and CSC markers was associated with the poorest prognosis, identifying a high-risk patient population. Combined FAK and paclitaxel treatment reduced tumour size, Ki67, ex-vivo mammospheres and ALDH+ expression in two triple negative patient derived Xenograft (PDX) models. Combined treatment reduced tumour initiation in a limiting dilution re-implantation PDX model. Combined FAK inhibition with adjuvant therapy has the potential to improve breast cancer survival.