Low RUFY3 expression level is associated with lymph node metastasis in older women with invasive breast cancer.

PURPOSE: Sentinel lymph node biopsy is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogeneous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women. METHODS: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1903) and The Cancer Genome Atlas (TCGA, n = 1046) Pan-cancer study cohorts. RESULTS: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3-predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease-specific survival among older women. CONCLUSION: Older women with breast cancers who had low expression level of RUFY3 were more frequently diagnosed with LN-positive tumors, which translated into worse prognosis.

Why Do Older Women Avoid Breast Cancer Surgery? A Qualitative Analysis of Decision-Making Factors.

BACKGROUND: Few studies have explored why older women (≥70 years old) avoid breast cancer surgery. This study aimed to identify physician- and patient-perceived attitudes that influence the decision to avoid surgery among older women with invasive breast cancer. METHODS: Semi-structured in-depth interviews were conducted with multidisciplinary breast cancer specialists and older women (≥70 years old) with breast cancer who declined surgery. Transcripts were iteratively coded using a theoretical framework to guide identification of common themes. Thematic comparison was performed between patients and physicians. RESULTS: Ten breast cancer specialists and eleven patients participated. Physicians believed older women declined surgery because they did not perceive breast cancer as a life-threatening ailment compared to other medical comorbidities. Physicians did not discuss breast reconstruction, as it was perceived to be unimportant. Treatment side effects, length of treatment, impact on quality of life, and minimal survival benefit strongly influenced patients' decision to decline surgery. Patients valued independence and quality of life over quantity of life. Patients felt empowered to participate in the decision-making process but appreciated having support. Both phyisicians and patients had congruent beliefs with respect to age impacting treatment decision, cosmesis playing a minor factor in treatment decisions, and importance of quality of life; however, they were discordant in their perceptions about the amount of support that patients have from their families. CONCLUSIONS: The decision to avoid surgery in older women stems from a variety of individual beliefs. Acknowledging patient values early in treatment planning may facilitate a patient-centered approach to the decision-making process.

Does oncoplastic surgery increase immediate (30-day) postoperative complications? An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

PURPOSE: Although there has been a significant increase in the use of oncoplastic surgery (OPS), data on the postoperative safety of this approach are limited compared to traditional lumpectomy. This study aimed to compare the immediate (30-day) postoperative complications associated with OPS and traditional lumpectomy. METHODS: An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was performed on women with breast cancer who underwent OPS or traditional lumpectomy. Logistic regression was used to explore the effect of type of surgery on the outcome of interest. RESULTS: A total of 109,487 women were analyzed of whom 8.3% underwent OPS. OPS had a longer median operative time than traditional lumpectomy. The unadjusted immediate (30-day) overall complication rate was significantly higher with OPS than traditional lumpectomy (3.8% versus 2.6%, p < 0.001). After adjusting for baseline differences, overall 30-day postoperative complications were significantly higher amongst women undergoing OPS compared with traditional lumpectomy (OR 1.41, 95%CI 1.24-1.59). Factors that were independent predictors of overall 30-day complications included higher age, higher BMI, race, smoking status, lymph node surgery, neoadjuvant chemotherapy, ASA class ≥ 3, in situ disease, and year of operation. The interaction term between type of surgery and operative time was not statistically significant, indicating that operative time did not modify the effect of type of surgery on immediate postoperative complications. CONCLUSIONS: Although there were slightly higher overall complication rates with OPS, the absolute rates remained quite low for both groups. Therefore, OPS may be performed in women with breast cancer who are suitable candidates.

Screening women at high risk for breast cancer: one program fits all? : Subgroup analysis of a large population high risk breast screening program.

INTRODUCTION: The Ontario High Risk Breast Screening program follows women aged 30-69 at an increased risk of breast cancer, using a yearly mammography and breast MRI. The aim of this study is to determine the clinical outcomes for the enrolled women. METHODS: Observational cohort study following 2081 participants in the high-risk screening program 2011-2017. The participants were divided into three subgroup according to their risk criteria: (a) known carriers of pathogenic variants (PV) in hereditary breast cancer genes. (b) Previous chest radiotherapy. (c) Estimated life time risk (ELR) ≥ 25%, calculated using the International Breast Cancer Intervention Study (IBIS) tool, with no known mutation or previous radiation. All Breast Cancer (BC) diagnosed during the follow-up time were recorded. RESULTS: 673 women carried PVs in hereditary breast cancer genes, 159 had a history of chest radiotherapy, and 1249 had an ELR ≥ 25%. The total cohort of screening years was 8126. Median age at BC diagnosis was 41 for the first group, 47 for the second group and 51 for the third. BC incidence rate was 18.2 for PV mutation carriers, 17.9 for the chest radiotherapy group and 6.2 for ELR ≥ 25%. Hazard ratio was similar for the first two groups, but significantly lower for the ELR ≥ 25% group. When stratifying by age, the incidence rate in the ELR ≥ 25% increased over time, until it became similar to that of the other subgroups after age 50. CONCLUSION: Our findings question the need to screen women with an elevated lifetime risk using the same screening practices used for women who are PV mutation carriers, or with a history of chest radiation, prior to the age of 50.

Improving the competency of medical students in clinical breast examination through a standardized simulation and multimedia-based curriculum.

PURPOSE: Clinical breast examination (CBE) is an important step in the assessment of patients with breast-related complaints. We developed a standardized simulation and multimedia-based (SSMBI) curriculum using current evidenced-based recommendations. This study aimed to determine if SSMBI training resulted in better performance (examination scores and detection of abnormal findings) than the traditional teaching method. METHODS: Novice fourth-year medical students were exposed to the SSMBI curriculum (n = 68) or traditional (n = 52) training. The traditional group was taught by a lecture and attending weekly clinics where they had hands-on experience. The SSMBI group underwent a structured lecture followed by an instructional video and dedicated simulated teaching. Both groups were assessed through a written knowledge exam and an objective structured clinical examination (OSCE). Student's t test and χ2 tests were used to assess differences in CBE technique and knoweldge. RESULTS: Students who underwent SSMBI training had significantly higher numbers of correct answers describing the different steps and justifications of CBE. OSCE performance was significantly higher in the SSMBI group. SSMBI-trained students were more likely to complete all the necessary CBE steps compared to traditionally-trained students (88.2% vs. 28.2%, p < 0.00001). The SSMBI group was also more systematic and more likely to perform adequate inspection, palpation, examination of the nipple-areolar complex, and identify and characterize a palpable lesion (p < 0.05). CONCLUSIONS: Formal SSMBI training is an important asset when teaching medical students how to perform a CBE. Real clinical experience is still necessary to refine this skill and the physician-patient interaction.

Is immediate breast reconstruction safe in women over 70? An analysis of the National Surgical Quality Improvement Program (NSQIP) database.

PURPOSE: The safety of immediate breast reconstruction (IBR) in older women is largely unknown. This study aimed to determine the 30-day postoperative complication rates following IBR (implant-based or autologous) in older women (≥ 70 years) with breast cancer and to compare them to younger women (18-69 years). METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used to identify women with in situ or invasive breast cancer who underwent IBR (2005-2016). Outcomes included 30-day postoperative morbidity and mortality, which were compared across age groups stratified by type of reconstruction. RESULTS: Of 28,850 women who underwent implant-based and 9123 who underwent autologous reconstruction, older women comprised 6.5% and 5.7% of the sample, respectively. Compared to younger women, older women had more comorbidities, shorter operative times, and longer length of hospital stay. In the implant-based reconstruction group, the 30-day morbidity rate was significantly higher in older women (7.5% vs 5.3%, p < 0.0001) due to higher rates of infectious, pulmonary, and venous thromboembolic events. Wound morbidity and prosthesis failure occurred equally among age groups. In the autologous reconstruction group, there was no statistically significant difference in the 30-day morbidity rates (older 9.5% vs younger 11.6%, p = 0.15). Both wound morbidity and flap failure rates were similar between the two age groups. For both reconstruction techniques, mortality within 30 days of breast surgery was rare. CONCLUSION: Immediate breast reconstruction is safe in older women. These data support the notion that surgeons should discuss IBR as a safe and integral part of cancer treatment in well-selected older women.

Patient-reported factors influencing the treatment decision-making process of older women with non-metastatic breast cancer: a systematic review of qualitative evidence.

PURPOSE: Older women (≥ 70 years old) with breast cancer undergo different treatments than young women. Studies have examined factors that influence this disparity, but synthesized patient-reported data are lacking in the literature. This study aims to identify, appraise, and synthesize the existing qualitative evidence on patient-reported factors influencing older women's decision to accept or decline breast cancer treatment. METHODS: A systematic review was performed in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA) principles. Medline, Embase, CINAHL, and PsycINFO were searched for qualitative studies describing patient-reported factors influencing the decision-making process of older women (≥ 70 years old) with non-metastatic invasive breast cancer. Quality was assessed using the Standards for Reporting Qualitative Research (SRQR) criteria. Common ideas were coded, thematically organized, and synthesized within a theoretical framework. RESULTS: Of 5998 studies identified, 10 met eligibility criteria. The median SRQR total score was 13.04 (IQR 12.84-13.81). The studies represented a range of cancer treatments; most of the studies focused on surgery and primary endocrine therapy. Our data show that the most common patient-reported factors in the decision-making process included treatment characteristics, personal goals/beliefs, patient characteristics, physician's recommendation, and personal/family experience. These factors led the patient to either accept or decline treatment, and were not consistent across all studies included. Studies used different interview guides, which may have affected these results. CONCLUSIONS: This systematic review highlights the complexity of factors that influence an older woman's treatment decision-making process. Acknowledging and addressing these factors may improve discussions about treatment choices between older women and their health care providers, and encourage maximization of a patient-centered approach.

Thirty-day postoperative morbidity and mortality in elderly women with breast cancer: an analysis of the NSQIP database.

PURPOSE: Postoperative complication rates for elderly women undergoing breast cancer surgery have not been well studied. We describe the postoperative complication rates of elderly (≥ 70 years) women with breast cancer and compare them with young (40-69 years) women. METHODS: Data were extracted from the National Surgical Quality Improvement Program database (2004-2014). We included women with invasive breast cancer who underwent surgery. Outcomes were 30-day postoperative morbidity and mortality (complications), which were compared between young and elderly women. Morbidity was categorized using the Surgical Risk Preoperative Assessment System (SURPAS) clusters. RESULTS: We identified 100,037 women of which 26.7% were elderly. Compared to young women, elderly women were more likely to have more comorbidities and undergo breast-conserving surgery, but less likely to undergo lymph node surgery, breast reconstruction, and neoadjuvant chemotherapy. While the 30-day overall morbidity rate was not significantly different between young and elderly women (3.9 vs. 3.8%, p = 0.2), elderly women did have significantly higher rates of pulmonary, cardiac (arrest and myocardial infarction), venous thromboembolic, and neurological morbidity. Specific morbidities that showed significantly lower rates among elderly women included wound disruption and deep and organ space surgical site infection. Any cause death was significantly higher in elderly compared to young women (0.2 vs. 0.05%, p < 0.001). CONCLUSIONS: While some specific 30-day postoperative morbidities were more often seen in elderly women, the overall 30-day postoperative complication rate was very low. These data support the safety of breast cancer surgery in well-selected elderly patients.

Management of complex polyps of the colon and rectum.

PUPRPOSE: Benign polyps that are technically challenging and unsafe to remove via polypectomy are known as complex polyps. Concerns regarding safety and completeness of resection dictate they undergo advanced endoscopic techniques, such as endoscopic mucosal resection or surgery. We provide a comprehensive overview of complex polyps and current treatment options. METHODS: A review of the English literature was conducted to identifyarticles describing the management of complex polyps of the colon and rectum. RESULTS: Endoscopic mucosal resection is the standard of care for the majority of complex polyps. Only polyps that fail endoscopic mucosal resection or are highly suspicious of invasive cancer but which cannot be removed endoscopically warrant surgery. CONCLUSION: Several factors influence the treatment of a complex polyp; therefore, there cannot be a "one-size-fitsall" approach. Treatment should be tailored to the lesion's characteristics, the risk of adverse events, and the resources available to the treating physician.

Trabectedin for inoperable or recurrent soft tissue sarcoma in adult patients: a retrospective cohort study.

BACKGROUND: Trabectedin is an antineoplastic agent used for patients with soft tissue sarcoma (STS) who fail standard-of-care treatment. Real-world data of its performance is scarce. This study evaluates the safety and effectiveness of trabectedin for patients with advanced STS who were treated at a high-volume sarcoma center. METHODS: A retrospective chart review was performed on 77 patients treated with trabectedin (24 h infusion q3w) between 01/2005 and 05/2014. Data regarding safety, objective radiological response, progression-free and overall survival were analyzed. RESULTS: Median age at treatment onset was 52y [interquartile range (IQR): 45-61y]. Tumors included leiomyosarcoma (41.6%), liposarcoma (18.2%), and synovial sarcoma (13%). Trabectedin was provided as ≥ third-line chemotherapy in 71.4%. Median number of cycles was 2 (range: 1-17). Dose reduction and treatment delays occurred in 19.5 and 40.3%, respectively. Toxicities occurred in 78%, primarily for neutropenia or elevated liver enzymes. Two patients died secondary to trabectedin-induced rhabdomyolysis. Treatment was discontinued because of disease progression (84.7%), toxicity (10%), and patient preference (5%). Partial response or stable disease occurred in 14.1 and 33.8%, respectively, while 52.1% developed progressive disease. Median progression-free survival was 1.3 m (IQR: 0.7-3.5 m) and was significantly higher in patients lacking severe toxicities or progressive disease. Median overall survival was 6.7 m (IQR: 2.3-12.7 m) and was significantly higher in patients with leiomyosarcoma or liposarcoma relative to other histologies. CONCLUSIONS: Trabectedin has an acceptable safety profile as an anti-tumor agent. Our data further suggest there may be some benefit in using trabectedin particularly in patients with leiomyo- or liposarcoma who failed standard-of-care agents.

Tumor vascularization is critical for oncolytic vaccinia virus treatment of peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) represents a significant clinical challenge for which there are few treatment options. Oncolytic viruses are ideal candidates for PC treatment because of their high tumor specificity, excellent safety profile and suitability for peritoneal delivery. Here, we described the use of vvDD-SR-RFP, a recombinant vaccinia virus, in xenograft and syngeneic models of colorectal PC. Colorectal cancer cell lines were highly susceptible to vvDD-SR-RFP replication and cytotoxicity. Intraperitoneal delivery of vvDD-SR-RFP on Day 12 to mice with colorectal carcinomatosis significantly improved survival whereas survival was not improved following virus treatment on Day 8, when tumors were smaller. Immunohistochemistry revealed early tumors had a poorly distributed network of blood vessels and lower proliferation index compared to later tumors. Virus infection was also restricted to tumor rims following Day 8 treatment, whereas it was disseminated in tumors treated on Day 12. Additionally, direct infection of tumor endothelium was observed and virus infection correlated with a loss of endothelial staining and induction of cell death. Our results demonstrate that tumor vasculature has a critical role in virus delivery and tumor response. This will have significant implications in the clinical setting, both in understanding timing of therapies and in designing combination treatment strategies.

Oncolytic vaccinia virus as an adjuvant treatment to cytoreductive surgery for malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Oncolytic viruses are a promising new therapy for cancer because of their ability to kill tumor cells with minimal toxicity to normal tissues. This experimental study aimed to examine the potential of modified vaccinia virus (VV) to treat MPM when administered alone or as an adjuvant treatment to surgery. METHODS: Two aggressive murine mesothelioma cell lines (AC29, AB12), were used. Cell viability and viral cytopathic effects were assessed using MTS and crystal violet assays. Immunocompetent mice were injected intraperitoneally with MPM cells and treated with intraperitoneal VV. Tumor-bearing mice also underwent cytoreductive surgery (CRS) followed by VV (or control) therapy. RESULTS: The cytotoxic effects of VV on MPM cell lines was significantly increased compared with the control non-cancer cell line. In both orthotopic models, VV induced tumor regression, prolonging median and long-term survival. VV treatment after incomplete CRS was not superior to VV alone; however, when mice with microscopic disease were treated with VV, further prolongation of median and long-term survivals was observed. CONCLUSIONS: VV selectively kills MPM cells in vitro and leads to improved survival and cures in immunocompetent murine models. Higher efficacy of the virus in the microscopic disease context suggests the use of the virus as an adjuvant treatment to complete surgical resection. These promising results justify further studies of VV in humans as a novel treatment for MPM.

Assessing patterns of practice of sentinel lymph node biopsy for breast cancer in Latin America.

INTRODUCTION: There is a lack information regarding how sentinel lymph node biopsy (SLNB) for breast cancer is carried out today in developing countries and how it was adapted. To rectify this situation we performed a pattern-of-practice survey amongst practicing surgeons in Latin America (LA). METHODS: A survey was developed to assess current surgical practice in breast cancer, use of SLNB, limitations to the implementation, training, technique variations, and observed adverse events. A total of 30 surgical associations and breast surgery societies in 18 Latin American countries were invited to participate. Surveys were distributed among member of these associations and 76.7 % of those contacted answered the survey. Responses were limited only to those who reported treating breast cancer patients. RESULTS: A total of 463 surgeons who manage breast cancer responded. Over 53 % of surgeons do not have sub-specialty training. Only 47.7 % have a high-volume case load, of which 87.8 % routinely perform SLNB. The main limitations perceived to the implementation of SLNB were a lack of resources/equipment (48 %) and training opportunities (33 %). Over 60 % reported that fewer than half of their patients were eligible for SLNB and 67.8 % reported that they were involved in teaching this technique to residents. CONCLUSIONS: A significant proportion of surgeons that treat breast cancer cases in LA have not had sub-specialty training or manage a low volume of cases. Among those surgeons with a high-volume caseload, SLNB is routinely performed. SLNB training during residency represents an opportunity for improvement in the region.

Locally-advanced primary neuroendocrine carcinoma of the breast: case report and review of the literature.

BACKGROUND: Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor. CASE PRESENTATION: We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neoadjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis. CONCLUSION: The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.

Quality indicators for sentinel lymph node biopsy: is there room for improvement?

BACKGROUND: Eleven quality indicators (QI) for sentinel lymph node biopsy (SLNB) were previously developed through a consensus-based approach, yet still need to be incorporated into clinical practice. We sought to evaluate the applicability and clinical relevance for surgeons. METHODS: Breast cancer patients undergoing SLNB between 2004 and 2008 at Mount Sinai Hospital, Toronto, were evaluated. Clinical and pathological data were obtained from an institutional database. Information on axillary recurrences was obtained through a retrospective chart review. Adherence to standardized protocols was evaluated in each case. RESULTS: All 11 QIs were measurable in 300 patients. The identification rate was 100%. More than 1 SLN was identified in 78.6% of patients. The SLNB was performed simultaneously with primary surgery in 96.7% of patients; 61 SLNs harboured metastasis. Of these patients, 80.3% underwent completion lymphadenectomy. Cases complied with protocols for radiocolloid injection and pathologic SLN evaluation/reporting. No ineligible patients underwent SLNB. Of patients with a complete 5-year follow-up (n = 42), only 1 had axillary recurrence. CONCLUSION: Applying QIs for SLNB was feasible, but modifications were necessary to develop a more practical approach to quality assessment. Of the 11 suggested QIs, those that encompass protocols (nuclear medicine and pathology) should be reclassified as prerequisites, as they are independent of the technical aspect of SLNB performance. The remaining 8 QIs encompass surgery per se and should be measured routinely by surgeons. Furthermore, concise and clinically relevant target rates are necessary for these QIs to be established as widely recognized control standards.

Vaccinia virus and peptide-receptor radiotherapy synergize to improve treatment of peritoneal carcinomatosis.

Tumor-specific overexpression of receptors enables a variety of targeted cancer therapies, exemplified by peptide-receptor radiotherapy (PRRT) for somatostatin receptor (SSTR)-positive neuroendocrine tumors. While effective, PRRT is restricted to tumors with SSTR overexpression. To overcome this limitation, we propose using oncolytic vaccinia virus (vvDD)-mediated receptor gene transfer to permit molecular imaging and PRRT in tumors without endogenous SSTR overexpression, a strategy termed radiovirotherapy. We hypothesized that vvDD-SSTR combined with a radiolabeled somatostatin analog could be deployed as radiovirotherapy in a colorectal cancer peritoneal carcinomatosis model, producing tumor-specific radiopeptide accumulation. Following vvDD-SSTR and 177Lu-DOTATOC treatment, viral replication and cytotoxicity, as well as biodistribution, tumor uptake, and survival, were evaluated. Radiovirotherapy did not alter virus replication or biodistribution, but synergistically improved vvDD-SSTR-induced cell killing in a receptor-dependent manner and significantly increased the tumor-specific accumulation and tumor-to-blood ratio of 177Lu-DOTATOC, making tumors imageable by microSPECT/CT and causing no significant toxicity. 177Lu-DOTATOC significantly improved survival over virus alone when combined with vvDD-SSTR but not control virus. We have therefore demonstrated that vvDD-SSTR can convert receptor-negative tumors into receptor-positive tumors and facilitate molecular imaging and PRRT using radiolabeled somatostatin analogs. Radiovirotherapy represents a promising treatment strategy with potential applications in a wide range of cancers.

Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice.

BACKGROUND: Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. METHODS: An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. RESULTS: The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). CONCLUSION: Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery.

Primary Care Physicians' Perspectives in Leading Breast Cancer Follow-Up Care.

INTRODUCTION: Limited data exist on the barriers associated with transitioning breast cancer follow-up care to primary care physicians (PCPs). This study aimed to describe the current perspectives of PCPs in managing breast cancer follow-up. METHOD: An online survey was distributed to PCPs in Toronto, ON, Canada. Questions examined PCPs' view of transitioning breast cancer follow-up care to their practices. RESULTS: Of 800 PCPs invited, 126 responded (response rate: 15.7%). The types of practice models amongst respondents included blended capitation (42.9%), blended salary (27%), and fee-for-service (17.5%). Seventy-seven percent of respondents stated they provided follow-up care. Approximately half of the respondents stated they were somewhat comfortable providing follow-up care. PCP-led follow-up care was considered either very (49.2%) or somewhat appropriate (30.2%). When asked about financial remuneration, 43.7% of respondents stated it was somewhat important. The factors that influenced the feasibility of PCP-led follow-up care included receipt of a detailed follow-up care plan provided by the specialist after discharge (81%), the ability to re-refer to specialists rapidly (56.3%), and the ability to obtain regular updates of best practice changes (59.5%). The preferred means of educational updates included E-mail (40.5%), continuing medical education events (30.2%), and electronic medical records (19.8%). When the fee model was taken into consideration there was no significant difference in opinions regarding follow-up care. CONCLUSIONS: Transitioning to a PCP-led model was supported by most of the PCPs who participated in this study. Their perspective on PCP-led follow up care and barriers associated with implementation of this model of care needs to be further explored with future studies that include larger sample size and a more diverse PCP population.

De-Escalating the Management of In Situ and Invasive Breast Cancer.

It is necessary to identify appropriate areas of de-escalation in breast cancer treatment to minimize morbidity and maximize patients' quality of life. Less radical treatment modalities, or even no treatment, have been reconsidered if they offer the same oncologic outcomes as standard therapies. Identifying which patients benefit from de-escalation requires particular care, as standard therapies will continue to offer adequate cancer outcomes. We provide an overview of the literature on the de-escalation of treatment of ductal carcinoma in situ (DCIS), local treatment of breast cancer, and surgery after neoadjuvant systemic therapy. De-escalation of breast cancer treatment is a key area of investigation that will continue to remain a priority. Improvements in understanding the natural history and biology of breast cancer, imaging modalities, and adjuvant treatments will expand this even further. Future efforts will continue to challenge us to consider the true role of various treatment modalities.

A Novel Three-Gene Score as a Predictive Biomarker for Pathologically Complete Response after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Although triple-negative breast cancer (TNBC) typically responds better to neoadjuvant chemotherapy (NAC) compared to the other subtypes, a pathological complete response (pCR) is achieved in less than half of the cases. We established a novel three-gene score using genes based on the E2F target gene set that identified pCR after NAC, which showed robust performance in both training and validation cohorts (total of n = 3862 breast cancer patients). We found that the three-gene score was elevated in TNBC compared to the other subtypes. A high score was associated with Nottingham histological grade 3 in TNBC. Across multiple cohorts, high-score TNBC enriched not only E2F targets but also G2M checkpoint and mitotic spindle, which are all cell proliferation-related gene sets. High-score TNBC was associated with homologous recombination deficiency, high mutation load, and high infiltration of Th1, Th2, and gamma-delta T cells. However, the score did not correlate with drug sensitivity for paclitaxel, 5-fluorouracil, cyclophosphamide, and doxorubicin in TNBC human cell lines. High-score TNBC was significantly associated with a high rate of pCR not only in the training cohort but also in the validation cohorts. High-score TNBC was significantly associated with better survival in patients who received chemotherapy but not in patients who did not receive chemotherapy. The three-gene score is associated with a high mutation rate, immune cell infiltration, and predicts response to NAC in TNBC.