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Purpose: This study was designed to determine (1) rates of clinically meaningful tumor reduction in breast tumor size following neoadjuvant chemotherapy (NAC), (2) which receptor subtypes and MRI phenotypes are associated with clinically meaningful tumor r

© 2013 Campbell et al.Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes.

Early detection of pregnancy is vital for appropriate reproductive management programmes to facilitate the rapid re-insemination of non-pregnant females and reduce the calving interval.

Penelitian ini bertujuan untuk menganalisa karakteristik getaran pada material komposit seratbambu dengan variasi penempatan posisi penggetar dan arah serat. Metode yang digunakandalam penelitian ini yaitu metode lamina, serat disusun tiga lapis dengan variasi arah 00/00/00,00/300/00 dan 300/00/300, sedangkan untuk metode analisa data adalah metode Euler-Bernoulli, data karakteristik getaran ditentukkan pada posisi penggetar 10 cm, 20 cm, 30 cm,40 cm, dan 50 cm. Hasil penelitian menunjukkan bahwa Kekakuan specimen akibat perubahanpenempatan posisi penggetar pada setiap specimen dengan arah serat yang berbeda adalah13.571 N/m dan 1099.227 N/m untuk arah serat 00/00/00, 44.208 N/m dan 3580.842 N/m untukarah serat 00/300/00 serta 38.387 N/m dan 3109.334 N/m untuk arah serat 300/00/300.Amplitudo maksimum yang terjadi diperoleh pada serat dengan arah 00/00/00 yaitu 0.000670 mdan minimumnya -0.000487 m pada sepesimen dengan arah serat 300/00/300. Nilai frekwensinatural (?n) material komposit serat bambu dipengaruhi oleh arah serat dan modulus elastisitasbahan, dimana untuk serat dengan arah 00/00/00 nilai frekwensi natural (?n) maksimumnya49.534 rad/s dan minimum 5.504 rad/s, dan serat dengan arah 00/300/00 nilai frekwensi natural(?n) maksimumnya 97.849 rad/s dan minimum 10.872 rad/s serta serat dengan arah300/00/300 nilai frekwensi natural (?n) maksimumnya 53.573 rad/s.Kata kunci: Serat bambu, posisi penggetar, karakteristik getaran, metode Euler-Bernoulli. This study aimed to analyze the vibration characteristics of the bamboo fiber composite materialwith a variation of positioning of the vibrator and the direction of the fiber. The method used inthis research is the method of lamina, fiber composed of three layers with variations of thedirection of 0o/0o/0o, 0o/30o/00 and 30o/0o/30o,whereas for data analysis method is the method ofEuler-Bernoulli. The characteristic of data vibration was determined in the positions vibrator of10 cm, 20 cm, 30 cm, 40 cm, and 50 cm. The results showed that the specimens rigidity due tochanges in the positioning of the vibrator on each specimen with different fiber direction is 13571 N / m and 1099,227 N / m for the direction of the fiber 0o/0o/0o, 44 208 N / m and 3580,842N / m for the fiber direction 0o/30o/0o and 38 387 N / m and 3109,334 N / m for fiber direction30o/0o/30o. The maximum amplitude occurs with the direction of fibers obtained on 0o/0o/0o thatthe minimum -0.000487 0.000670 m and m on specimen with 30o/0o/30o fiber direction. Thevalue of natural frequency (?n) bamboo fiber composite material is influenced by the directionof the fiber and the modulus of elasticity of the material, where the fiber with the direction of0o/0o/0o the value of natural frequency (?n) maximum 49 534 rad / s and a minimum of 5504rad / s, and fiber with directions 00/300/00 value of natural frequency (?n) maximum 97 849 rad/ s and a minimum of 10 872 rad / s as well as fiber to the direction 300/00/300 value of naturalfrequency (?n) maximum 53 573 rad / s.Keywords: Bamboo fiber, position vibrator, vibration characteristics, Euler-Bernoulli method.

New approaches are needed to determine which ductal carcinoma in situ (DCIS) is at high risk for progression to invasive ductal carcinoma (IDC). We retrospectively studied DCIS patients who declined surgery (2002-2019), and received endocrine therapy (ET) and breast MRI. Baseline MRI and changes at 3 months and 6 months were analyzed by recursive partitioning to stratify IDC risk. Sixty-two patients (63 DCIS; 1 bilateral) with a mean follow-up of 8.5 years were included. Fifty-one percent remained on active surveillance (AS) without evidence of IDC, with a mean duration of 7.6 years. A decision tree based on MRI features of lesion distinctness and background parenchymal enhancement (BPE) at baseline and change after 3 months of ET stratified patients into low, intermediate, and high risk for progression to IDC. MRI imaging features in patients treated with ET and undergoing AS, may help determine which DCIS lesions are at low versus high risk for IDC., (© 2024. The Author(s).)

This is a secondary data analysis of the TIPPING study, which included 1,121 patients with stage I-III breast cancer who had enumeration of CTCs (by either CellSearch or immunomagnetic enrichment and flow cytometry [IE/FC]) and disseminated tumor cells (DTCs) at the time of surgical resection between 1999 and 2012. The primary endpoint was mean number of CTCs by histology, taking into account method of detection and treatment type, and evaluation of histology specific prognostic cutpoints. Overall, patients with ILC had significantly higher CTC counts than those with IDC, a finding which persisted in the 382 patients with CTC enumeration by IE/FC method. Additionally, among those with primary surgery, patients with ILC had significantly higher mean CTC counts than those with IDC (mean 2.11 CTCs/mL versus 0.71 CTCs/mL respectively, p < 0.001), which persisted on multivariate analysis. Patients with ILC and CTC-high/DTC-high status trended towards reduced DRFS HR = 9.27, 95% CI 0.95-90.5, p = 0.055) and had significantly decreased BCSS (HR = 10.4, 95% CI 1.07-99.7, P = 0.043) compared with those who were CTC-low/DTC-low. In the IDC group, CTC-high/DTC-high status was not associated with either DRFS or BCSS. In neoadjvuantly treated patients, there was no significant difference in CTC counts in the ILC group versus the IDC group (mean 0.89 CTCs/mL versus 1.06 CTCs/mL respectively, p = 0.82). Our findings contribute to the limited literature on CTCs and DTCs in ILC, and suggest that clinical utility and optimal thresholds for CTC and DTC assays may differ by histologic subtype in early-stage breast cancer., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

While adjuvant treatment with the selective-estrogen receptor modulator (SERM) tamoxifen has been the standard of care for pre-menopausal patients with hormone receptor (HR) positive breast cancer, recent trials showed a benefit of aromatase inhibitors (AI) and ovarian function suppression (OFS) for some patients. The approach to endocrine therapy has not been well studied in pre-menopausal patients with invasive lobular carcinoma (ILC). We identified 202 pre-menopausal patients with HR positive stage I-III ILC in an institutional database. We investigated factors associated with endocrine therapy type and determined changes in systemic therapy from 1990-2021. We evaluated associations between endocrine therapy type and disease-free survival (DFS) with a multivariate Cox proportional hazards model. Of 202 patients, most (69.3%) were prescribed a SERM (99.3% tamoxifen). Those who received an AI had significantly higher stage disease. Over time, use of OFS and AI increased significantly in stage II or III cases (from 0% in 1990 to 56% after 2015 for stage II; from 0% to 80% after 2015 for stage III). Concurrently, adjuvant chemotherapy use significantly decreased in stage II cases (from 67% to 19%). In an exploratory multivariable model, longer duration of AI compared to tamoxifen was associated with significantly improved DFS (HR 0.31; 95% CI 0.11-0.86; p = 0.025). While most pre-menopausal patients received adjuvant tamoxifen, the use of OFS and AIs increased significantly over time. The association between AI use and improved DFS may be consistent with prior randomized trials and warrants further investigation into predictive factors to guide treatment selection., (© 2023. The Author(s).)

Background: Although investigators have shown associations between socioeconomic status (SES) and outcomes in breast cancer, there is a paucity of such data for invasive lobular carcinoma (ILC), the second most common type of breast cancer. Herein we evaluated the relationship between SES with tumor features and outcomes in stage I to III patients with ILC., Methods: We analyzed a prospectively maintained institutional ILC database and utilized the area deprivation index (ADI) to determine neighborhood adversity, an indicator of SES. We used Cox proportional hazards models in Stata 17.0 to evaluate relationships between ADI quintile (Q), race, body mass index (BMI), clinicopathologic features, treatment type, and event-free survival (EFS)., Results: Of 804 patients with ILC, 21.4% lived in neighborhoods classified as ADI Q1 (least resource-deprived) and 19.7% in Q5 (most resource-deprived). Higher deprivation was significantly associated with larger tumor size (3.6 cm in Q5 vs. 3.1 cm in Q1), increased presence of lymphovascular invasion (8.9% in Q5 vs. 6.7% in Q1), and decreased use of adjuvant endocrine therapy (67.1% in Q5 vs. 73.6% in Q1). On multivariable analysis, tumor size, receptor subtypes, and omission of adjuvant endocrine therapy were associated with reduced EFS., Conclusions: These data show that patients with ILC and higher ADI experience more aggressive tumors and differences in treatment. More data evaluating the complex relationships between these factors is needed to optimize outcomes for patients with ILC, regardless of SES., Impact: ADI is associated with differences in patients with ILC., (©2023 The Authors; Published by the American Association for Cancer Research.)

Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a histologic, immunohistochemical, genetic, and clinicopathologic assessment of 42 invasive TNACs (1 with a focal spindle cell component) from 41 patients, 2 pure apocrine ductal carcinomas in situ (A-DCIS), and 1 A-DCIS associated with spindle cell metaplastic carcinoma (SCMBC). All TNACs had characteristic apocrine morphology and expressed androgen receptor (42/42), gross cystic disease fluid protein 15 (24/24), and CK5/6 (16/16). GATA3 was positive in most cases (16/18, 89%), and SOX10 was negative (0/22). TRPS1 was weakly expressed in a minority of tumors (3/14, 21%). Most TNACs had low Ki67 proliferation (≤10% in 67%, 26/39), with a median index of 10%. Levels of tumor infiltrating lymphocytes were low (≤10% in 93%, 39/42, and 15% in 7%, 3/42). Eighteen percent of TNACs presented with axillary nodal metastasis (7/38). No patients treated with neoadjuvant chemotherapy achieved pathologic complete response (0%, 0/10). Nearly all patients with TNAC (97%, n = 32) were without evidence of disease at the time of study (mean follow-up of 62 months). Seventeen invasive TNACs and 10 A-DCIS (7 with paired invasive TNAC) were profiled by targeted capture-based next-generation DNA sequencing. Pathogenic mutations in phosphatidylinositol 3-kinase pathway genes PIK3CA (53%) and/or PIK3R1 (53%) were identified in all TNACs (100%), including 4 (24%) with comutated PTEN. Ras-MAPK pathway genes, including NF1 (24%), and TP53 were mutated in 6 tumors each (35%). All A-DCIS shared mutations, such as phosphatidylinositol 3-kinase aberrations and copy number alterations with paired invasive TNACs or SCMBC, and a subset of invasive carcinomas showed additional mutations in tumor suppressors (NF1, TP53, ARID2, and CDKN2A). Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Development of the nipple-sparing mastectomy (NSM) technique has dramatically improved breast reconstruction, and preservation of the nipple-areolar complex (NAC) positively influences patient satisfaction. However, women with large, ptotic breasts have historically not been candidates for NAC preservation due to impaired perfusion of the NAC leading to NAC loss. Although reduction mammoplasty has been reported as a strategy to increase candidacy for NSM, success rates and surgical outcomes for this staged approach are not well described in heterogeneous clinical scenarios., Methods: We performed a retrospective chart review of all patients who underwent reduction mammoplasty followed by NSM at our institution between January 2014 and September 2020. Clinical and surgical characteristics were collected. All surgical complications, including NAC loss rates, were analyzed., Results: Forty-one patients (74 breasts) underwent staged NSM during the defined time period. The average time between breast reduction mammoplasty and NSM was 213 days. Overall, 94.6% of NSM resulted in successful nipple preservation. There was no significant difference in the time interval from breast reduction mammoplasty to NSM between patients who had NAC loss (208 days) and those who did not (213 days, P = 0.87). Increasing age was significantly associated with risk of NAC loss ( P = 0.002) in our cohort., Conclusions: In women with breast ptosis (which precludes safe NSM), it is possible to first offer reduction mammoplasty to preserve the NAC for future NSM. Our data suggest that 3 months between staged procedures is a safe time frame., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Ductal carcinoma in situ (DCIS) is a biologically heterogenous entity with uncertain risk for invasive ductal carcinoma (IDC) development. Standard treatment is surgical resection often followed by radiation. New approaches are needed to reduce overtreatment. This was an observational study that enrolled patients with DCIS who chose not to pursue surgical resection from 2002 to 2019 at a single academic medical center. All patients underwent breast MRI exams at 3- to 6-month intervals. Patients with hormone receptor-positive disease received endocrine therapy. Surgical resection was strongly recommended if clinical or radiographic evidence of disease progression developed. A recursive partitioning (R-PART) algorithm incorporating breast MRI features and endocrine responsiveness was used retrospectively to stratify risk of IDC. A total of 71 patients were enrolled, 2 with bilateral DCIS (73 lesions). A total of 34 (46.6%) were premenopausal, 68 (93.2%) were hormone-receptor positive, and 60 (82.1%) were intermediate- or high-grade lesions. Mean follow-up time was 8.5 years. Over half (52.1%) remained on active surveillance without evidence of IDC with mean duration of 7.4 years. Twenty patients developed IDC, of which 6 were HER2 positive. DCIS and subsequent IDC had highly concordant tumor biology. Risk of IDC was characterized by MRI features after 6 months of endocrine therapy exposure; low-, intermediate-, and high-risk groups were identified with respective IDC rates of 8.7%, 20.0%, and 68.2%. Thus, active surveillance consisting of neoadjuvant endocrine therapy and serial breast MRI may be an effective tool to risk-stratify patients with DCIS and optimally select medical or surgical management., Significance: A retrospective analysis of 71 patients with DCIS who did not undergo upfront surgery demonstrated that breast MRI features after short-term exposure to endocrine therapy identify those at high (68.2%), intermediate (20.0%), and low risk (8.7%) of IDC. With 7.4 years mean follow-up, 52.1% of patients remain on active surveillance. A period of active surveillance offers the opportunity to risk-stratify DCIS lesions and guide decisions for operative management., Competing Interests: R.A. Mukhtar reports other from Exact Sciences during the conduct of the study. G.L. Hirst reports she/her partner holds stock in Moderna, Nanostring, Gilead Sciences, and Exact Sciences which represents <1% of company value. None of these companies are involved in this described study. L.J. Esserman reports personal fees from Blue Cross Medical Advisory Panel; grants from Quantum Leap Healthcare Collaborative and Merck outside the submitted work. No disclosures were reported by the other authors., (© 2022 The Authors; Published by the American Association for Cancer Research.)

When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010-2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%, p < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma (p = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection., (© 2021. The Author(s).)

Enrollment in metastatic breast cancer trials usually requires measurable lesions, but patients with invasive lobular carcinoma (ILC) tend to form diffuse disease. We found that the proportion of patients with metastatic ILC enrolled in clinical trials at our institution was significantly lower than that of patients with invasive ductal carcinoma (IDC). Possible links between requiring measurable disease and decreased enrollment of ILC patients require further study to ensure equitable trial access., (© 2021. The Author(s).)

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers., (© 2021. The Author(s).)

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons' knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: While fibroadenomas are common in the general population, affecting 10-20% of women, they are rarely early-onset, multiple, and bilateral., Case Presentation: An 18-year-old woman presented with a 6 year history of multiple, bilateral breast masses without family history of breast disease. Magnetic resonance imaging (MRI, Fig. 1) of the breasts showed innumerable, bilateral breast masses ranging in size from 0.5 to 4 cm. Two needle biopsies showed fibroadenoma. Although the patient's family history did not meet National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, it was performed due to the rarity of her presentation. Genetic testing identified a pathogenic mutation in the phosphatase and tensin homolog (PTEN) gene., Conclusions: A germline mutation in PTEN is associated with an increased risk of breast cancer and often occurs as part of Cowden Syndrome. This case highlights the importance of genetic testing in patients with unusual presentations of early-onset, bilateral, and multiple (greater than four) fibroadenomas.

The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences. Based on the evidence, future recommendations will be provided. First, data on contralateral breast cancer risk and CPM rates and trends are addressed. After that, the evidence is structured around four main patient rationales for CPM formulated as questions that patients might ask their surgeon: Will CPM reduce mortality risk? Will CPM reduce the risk of contralateral breast cancer? Can I avoid future screening with CPM? Will I have better breast symmetry after CPM? Also, three different guidelines regarding CPM will be reviewed. Studies indicate a large gap between patient preferences for radical risk reduction with CPM and the current approaches recommended by important guidelines. We suggest a strategy including shared decision-making to enhance surgeons' communication with patients about contralateral breast cancer and treatment options, to empower patients in order to optimize the use of CPM incorporating accurate risk assessment and individual patient preferences., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Neoadjuvant therapy in breast cancer can downstage axillary lymph nodes and reduce extent of axillary surgery. As such, accurate determination of nodal status after neoadjuvant therapy and before surgery impacts surgical management. There are scarce data on the diagnostic accuracy of breast magnetic resonance imaging (MRI) for nodal evaluation after neoadjuvant therapy in patients with invasive lobular carcinoma (ILC), a diffusely growing tumor type. We retrospectively analyzed patients with stage 1-3 ILC who underwent pre-operative breast MRI after either neoadjuvant chemotherapy or endocrine therapy at our institution between 2006 and 2019. Two breast radiologists reviewed MRIs and evaluated axillary nodes for suspicious features. All patients underwent either sentinel node biopsy or axillary dissection. We evaluated sensitivity, specificity, negative and positive predictive values, and overall accuracy of the post-treatment breast MRI in predicting pathologic nodal status. Of 79 patients, 58.2% received neoadjuvant chemotherapy and 41.8% neoadjuvant endocrine therapy. The sensitivity and negative predictive value of MRI were significantly higher in the neoadjuvant endocrine therapy cohort than in the neoadjuvant chemotherapy cohort (66.7 vs. 37.9%, p = 0.012 and 70.6 vs. 40%, p = 0.007, respectively), while overall accuracy was similar. Upstaging from clinically node negative to pathologically node positive occurred in 28.0 and 41.7%, respectively. In clinically node positive patients, those with an abnormal post-treatment MRI had a significantly higher proportion of patients with ≥4 positive nodes on pathology compared to those with a normal MRI (61.1 versus 16.7%, p = 0.034). Overall, accuracy of breast MRI for predicting nodal status after neoadjuvant therapy in ILC was low in both chemotherapy and endocrine therapy cohorts. However, post-treatment breast MRI may help identify patients with a high burden of nodal disease (≥4 positive nodes), which could impact pre-operative systemic therapy decisions. Further studies are needed to assess other imaging modalities to evaluate for nodal disease following neoadjuvant therapy and to improve clinical staging in patients with ILC.

Women with dense breasts have an increased lifetime risk of malignancy that has been attributed to a higher epithelial density. Quantitative proteomics, collagen analysis, and mechanical measurements in normal tissue revealed that stroma in the high-density breast contains more oriented, fibrillar collagen that is stiffer and correlates with higher epithelial cell density. microRNA (miR) profiling of breast tissue identified miR-203 as a matrix stiffness-repressed transcript that is downregulated by collagen density and reduced in the breast epithelium of women with high mammographic density. Culture studies demonstrated that ZNF217 mediates a matrix stiffness- and collagen density-induced increase in Akt activity and mammary epithelial cell proliferation. Manipulation of the epithelium in a mouse model of mammographic density supported a causal relationship between stromal stiffness, reduced miR-203, higher levels of the murine homolog Zfp217, and increased Akt activity and mammary epithelial proliferation. ZNF217 was also increased in the normal breast epithelium of women with high mammographic density, correlated positively with epithelial proliferation and density, and inversely with miR-203. The findings identify ZNF217 as a potential target toward which preexisting therapies, such as the Akt inhibitor triciribine, could be used as a chemopreventive agent to reduce cancer risk in women with high mammographic density.

In recent years, neoadjuvant treatment trials have shown that breast cancer subtypes identified on the basis of genomic and/or molecular signatures exhibit different response rates and recurrence outcomes, with the implication that subtype-specific treatment approaches are needed. Estrogen receptor-positive (ER+) breast cancers present a unique set of challenges for determining optimal neoadjuvant treatment approaches. There is increased recognition that not all ER+ breast cancers benefit from chemotherapy, and that there may be a subset of ER+ breast cancers that can be treated effectively using endocrine therapies alone. With this uncertainty, there is a need to improve the assessment and to optimize the treatment of ER+ breast cancers. While pathology-based markers offer a snapshot of tumor response to neoadjuvant therapy, non-invasive imaging of the ER disease in response to treatment would provide broader insights into tumor heterogeneity, ER biology, and the timing of surrogate endpoint measurements. In this review, we provide an overview of the current landscape of breast imaging in neoadjuvant studies and highlight the technological advances in each imaging modality. We then further examine some potential imaging markers for neoadjuvant treatment response in ER+ breast cancers.

Rates of positive margins after surgical resection of invasive lobular carcinoma (ILC) are high (ranging from 18 to 60%), yet the efficacy of re-excision lumpReceptor subtypeectomy for clearing positive margins is unknown. Concerns about the diffuse nature of ILC may drive increased rates of completion mastectomy to treat positive margins, thus lowering breast conservation rates. We therefore determined the success rate of re-excision lumpectomy in women with ILC and positive margins after surgical resection. We identified 314 cases of stage I-III ILC treated with breast conserving surgery (BCS) at the University of California, San Francisco. Surgical procedures, pathology reports, and outcomes were analyzed using univariate and multivariate statistics and Cox-proportional hazards models. We evaluated outcomes before and after the year 2014, when new margin management consensus guidelines were published. Positive initial margins occurred in 118 (37.6%) cases. Of these, 62 (52.5%) underwent re-excision lumpectomy, which cleared the margin in 74.2%. On multivariate analysis, node negativity was significantly associated with successful re-excision (odds ratio [OR] 3.99, 95% CI 1.15-13.81, p  = 0.029). After 2014, we saw fewer initial positive margins (42.7% versus 25.5%, p  = 0.009), second surgeries (54.6% versus 20.2%, p  < 0.001), and completion mastectomies (27.7% versus 4.5%, p  < 0.001). In this large cohort of women with ILC, re-excision lumpectomy was highly successful at clearing positive margins. Additionally, positive margins and completion mastectomy rates significantly decreased over time. These findings highlight improvements in management of ILC, and suggest that completion mastectomy may not be required for those with positive margins after initial BCS., Competing Interests: Competing interestsThe authors declare no competing interests.

A 59-year-old woman with a history of cosmetic implants developed ipsilateral synchronous breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and invasive ductal carcinoma in the left breast. Each tumor was subjected to next-generation sequencing, and separate analyses revealed mutually exclusive aberrations: an activating STAT3 mutation in the lymphoma and a PIK3CA in-frame deletion in the carcinoma. The patient was treated with removal of implants, capsulectomy, partial mastectomy, sentinel node biopsy, radiotherapy, and endocrine therapy with no evidence of recurrence for 1 year. This case illustrates the importance of obtaining thorough evaluation for concomitant malignancies in the breast at the time of diagnosis of BIA-ALCL. Herein, we review the current recommendations for evaluation and management of BIA-ALCL.

Tumor associated macrophages (TAMs) are recruited from the circulation to the tumor site, and can undergo a spectrum of phenotypic changes, with two contrasting activation states described in the literature: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA(+) TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA(+) TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA(+) TAM levels were associated with more M1- than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA(+) TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA(+) TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA(+) TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA(+) TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer.

While several inflammatory cell types participate in cancer development, macrophages specifically play a key role in breast cancer, where they appear to be part of the pathogenesis of high-grade tumors. Tumor-associated macrophages (TAMs) produce factors that promote angiogenesis, remodel tissue and dampen the immune response to tumors. Specific macrophage types contribute to increased metastases in animal models, while human studies show an association between TAMs and tumors with poor prognostic features. Macrophages display a spectrum of phenotypic states, with the tumor microenvironment skewing TAMs towards a 'nonclassical' activation state, known as the M2, or wound healing/regulatory state. These TAMs are found in high-risk breast cancers, making them an important therapeutic target to explore. Improved techniques for identifying TAMs should translate into clinical applications for prognosis and treatment.

Annual volume of pancreatic resections has been shown to affect mortality rates, prompting recommendations to regionalize these procedures to high-volume hospitals. Implementation has been difficult, given the paucity of high-volume centers and the logistical hardships facing patients. Some studies have shown that low-volume hospitals achieve good outcomes as well, suggesting that other factors are involved. We sought to determine whether variations in annual volume affected patient outcomes in 511 patients who underwent pancreatic resections at the University of California, San Francisco between 1990 and 2005. We compared postoperative mortality and complication rates between low, medium, or high volume years, designated by the number of resections performed, adjusting for patient characteristics. Postoperative mortality rates did not differ between high volume years and medium/low volume years. As annual hospital volume of pancreatic resections may not predict outcome, identification of actual predictive factors may allow low-volume centers to achieve excellent outcomes.