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.

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.

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.

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.

Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC).

Patients with triple negative breast cancer (TNBC) have a poor prognosis. A novel prognostic biomarker may guide management by appropriately selecting patients for particular treatments. Peripheral blood neutrophil-to-lymphocyte ratio (NLR) was reported to associate with cancer progression, thus we hypothesized that intratumor genetic NLR will reflect tumor immune microenvironment (TIME) and breast cancer biology. The intratumoral genetic NLR previously defined as the ratio of CD66b (CEACAM8) and CD8 (CD8A) gene expressions was utilized to analyze total of 2,994 patients from METABRIC, TCGA, GSE21094, GSE22358, GSE25088, GSE32646, and GSE2603 cohorts. Intratumoral genetic NLR did not correlate with cancer stage nor clinical parameters of cancer cell proliferation such as Nottingham histological grade or MKI67 expression levels in neither the METABRIC or TCGA cohorts. Intratumoral genetic NLR-high breast cancer was not associated with pathologic complete response (pCR) after neoadjuvant chemotherapy in 5 independent cohorts with different regimens. Despite these results, intratumoral genetic NLR-high TNBC demonstrated worse disease-free, disease-specific, and overall survival. Intratumoral genetic NLR-low TNBC enriched multiple immune-related gene sets, was associated with higher favorable immune-related scores and with a favorable TIME, whereas no gene sets enriched to NLR-high TNBC. In conclusion, intratumoral genetic NLR-low TNBC was associated with favorable TIME and with better survival.

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.

A novel five-gene score to predict complete pathological response to neoadjuvant chemotherapy in ER-positive/HER2-negative breast cancer.

Neoadjuvant Chemotherapy (NAC) is not frequently used in ER-positive/HER2-negative breast cancer (BC) because around 10% patients achieve pathological complete response (pCR). Since NAC can result in cancer downstaging both in the breast and axilla and prevent a morbid surgery, thus a score to predict pCR in this population will be crucial to identify patients who can benefit from this approach. A total of 4038 patients from cohorts; GSE25066, GSE20194, Hess, GSE20181, TCGA-BRCA and METBRIC were analyzed. The score was generated by the 5 most highly expressed genes in the Hallmark E2F targets gene set amongst patients in the GSE25066 cohort with ER-positive/HER2-negative BC who achieved pCR. The area under the curve was significantly higher in the score than that for the E2F targets score. High score ER-positive/HER2-negative BCs were significantly associated with higher Nottingham pathological grade, AJCC cancer stage, MKI67 expression levels, intratumor heterogeneity, homologous recombination defects, mutation burden, neoantigen load, and infiltration of anti-cancer immune cells (CD4+, T helper type1, plasmacytoid dendritic cells, M1 macrophages). They also expressed lower abundance of stromal cells including fibroblasts, lymphatic endothelial cells, pericytes and adipocytes consistently in GSE25066, TCGA and METABRIC cohorts. All cell proliferation-related gene sets, G2M checkpoint, E2F targets, MYC targets v1 and v2, Mitotic Spindle, were strongly enriched in high score BCs consistently in 3 cohorts. The gene score was significantly associated with high pCR rate consistently in the GSE25066 (38%, P < 0.001), GSE20194 (16%, P = 0.006), and Hess cohort (23%, P = 0.037). In conclusion, the 5-gene score reflects cancer cell proliferation and immune cell infiltration, and predicts pCR after NAC in ER-positive/HER2-negative breast cancer.

Low expression of miR-195 is associated with cell proliferation, glycolysis and poor survival in estrogen receptor (ER)-positive but not in triple negative breast cancer.

MiR-195 is a tumor suppressive microRNA in breast cancer. Its clinical relevance remains debatable as it has only been studied via in vitro experiments or small cohort studies. We analyzed a total of 2,038 patients in the TCGA and METABRIC cohorts to assess whether low miR-195 expressing tumors are associated with aggressive cancer characteristics and poor prognostic outcomes. The median cutoff of miR-195 expression was used to split the groups into miR-195 high and low groups. Low miR-19 expressing tumors demonstrated high cell proliferating features by enriching the gene sets associated with cell proliferation, MKI67 expression and pathological grade. One-third of the top target miR-195 genes were related to cell proliferation. Low miR-195 expressing tumors were associated with both pro-cancerous and anti-cancerous immune cells. Low miR-195 expressing tumors were associated with enhanced glycolysis and poor survival in ER-positive tumors, but not other subtypes of breast cancer. In conclusion, low expression of miR-195 in ER-positive breast cancer was associated with enhanced cancer cell proliferation, glycolysis, and worse overall survival.

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.

Adipogenesis in triple-negative breast cancer is associated with unfavorable tumor immune microenvironment and with worse survival.

Cancer-associated adipocytes are known to cause inflammation; however, the role of adipogenesis, the formation of adipocytes, in breast cancer is unclear. We hypothesized that intra-tumoral adipogenesis reflects a different cancer biology than abundance of intra-tumoral adipocytes. The Molecular Signatures Database Hallmark adipogenesis gene set of gene set variant analysis was used to quantify adipogenesis. Total of 5,098 breast cancer patients in multiple cohorts (training; GSE96058 (n = 3273), validation; TCGA (n = 1069), treatment response; GSE25066 (n = 508) and GSE20194 (n = 248)) were analyzed. Adipogenesis did not correlate with abundance of adipocytes. Adipogenesis was significantly lower in triple negative breast cancer (TNBC). Elevated adipogenesis was significantly associated with worse survival in TNBC, but not in the other subtypes. High adipogenesis TNBC was significantly associated with low homologous recombination deficiency, but not with mutation load. High adipogenesis TNBC enriched metabolism-related gene sets, but neither of cell proliferation- nor inflammation-related gene sets, which were enriched to adipocytes. High adipogenesis TNBC was infiltrated with low CD8+ T cells and high M2 macrophages. Although adipogenesis was not associated with neoadjuvant chemotherapy response, high adipogenesis TNBC was significantly associated with low expression of PD-L1 and PD-L2 genes, and immune checkpoint molecules index. In conclusion, adipogenesis in TNBC was associated with cancer metabolism and unfavorable tumor immune microenvironment, which is different from abundance of adipocytes.

Angiogenesis is associated with an attenuated tumor microenvironment, aggressive biology, and worse survival in gastric cancer patients.

Angiogenesis is a cornerstone of cancer as it allows tumors to receive oxygen and nutrients. A high level of angiogenesis within a tumor may therefore be indicative of its aggressiveness. In this study, we examined this hypothesis in gastric cancer. Gene set variation analysis was used to measure the level of angiogenesis in tumors in 1,348 gastric cancer patients using the Hallmark_angiogenesis gene set to score tumor transcriptomes. As we predicted, there was a significant correlation between angiogenesis score and expression of angiogenesis-related genes. The score moderately correlated with abundance of vessel-related stromal cells, fibroblasts and chondrocytes in the tumor microenvironment (TME). Tumors with high score had low infiltration of T helper type 1 and 2 cells but a greater infiltration of M1 macrophages and dendritic cells. They also had enriched expression of gene sets for coagulation, hypoxia, epithelial mesenchymal transition (EMT), and TGF-ß signaling. High angiogenesis score was significantly associated with advanced AJCC stage and higher T- but not N-parameters in the TNM staging system. Patients with a high score also had shorter survival. In conclusion, bulk tumor transcriptome-based quantification of tumor angiogenesis using a computational algorithm may serve to identify patients with worse survival in gastric cancer.

Degree of Early Estrogen Response Predict Survival after Endocrine Therapy in Primary and Metastatic ER-Positive Breast Cancer.

Endocrine therapy is the gold-standard treatment for ER-positive/HER2-negative breast cancer. Although its clear benefit, patient compliance is poor (50-80%) due to its long administration period and adverse effects. Therefore, a predictive biomarker that can predict whether endocrine therapy is truly beneficial may improve patient compliance. In this study, we use estrogen response early gene sets of gene set enrichment assay algorithm as the score. We hypothesize that the score could predict the response to endocrine therapy and survival of breast cancer patients. A total of 6549 breast cancer from multiple patient cohorts were analyzed. The score was highest in ER-positive/HER2-negative compared to the other subtypes. Earlier AJCC stage, as well as lower Nottingham pathological grade, were associated with a high score. Low score tumors enriched only allograft rejection gene set, and was significantly infiltrated with immune cells, and high cytolytic activity score. A low score was significantly associated with a worse response to endocrine therapy and worse survival in both primary and metastatic breast cancer patients. The hazard ratio was double that of ESR1 expression. In conclusion, the estrogen response early score predicts response to endocrine therapy and is associated with survival in primary and metastatic breast cancer.

High Expression of NRF2 Is Associated with Increased Tumor-Infiltrating Lymphocytes and Cancer Immunity in ER-Positive/HER2-Negative Breast Cancer.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a key modifier in breast cancer. It is unclear whether NRF2 suppresses or promotes breast cancer progression. We studied the clinical relevance of NRF2 expression by conducting in silico analyses in 5443 breast cancer patients from several large patient cohorts (METABRIC, GSE96058, GSE25066, GSE20194, and GSE75688). NRF2 expression was significantly associated with better survival, low Nottingham pathological grade, and ER-positive/HER2-negative and triple negative breast cancer (TNBC). High NRF2 ER-positive/HER2-negative breast cancer enriched inflammation- and immune-related gene sets by GSEA. NRF2 expression was elevated in immune, stromal, and cancer cells. High NRF2 tumors were associated with high infiltration of immune cells (CD8+, CD4+, and dendritic cells (DC)) and stromal cells (adipocyte, fibroblasts, and keratinocytes), and with low fraction of Th1 cells. NRF2 expression significantly correlated with area under the curve (AUC) of several drug response in multiple ER-positive breast cancer cell lines, however, there was no significant association between NRF2 and pathologic complete response (pCR) rate after neoadjuvant chemotherapy in human samples. Finally, high NRF2 breast cancer was associated with high expression of immune checkpoint molecules. In conclusion, NRF2 expression was associated with enhanced tumor-infiltrating lymphocytes in ER-positive/HER2-negative breast cancer.

Older women's experience with breast cancer treatment: A systematic review of qualitative literature.

BACKGROUND: The experience of older women during breast cancer treatment is insufficiently described by quantitative studies. This study aimed to systematically review qualitative data describing factors that influence older women's (≥65 years old) experience with 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, CINAHL, PsycINFO, and EMBASE were searched (inception - 2020). Quality assessment of essential item reporting was performed using the Standards for Reporting Qualitative Research (SRQR) criteria. Common ideas were coded, thematically organized, and synthesized within a theoretical framework. RESULTS: Of 7,773 studies identified, twelve were included. The median SRQR score was 13.4 (range 11.3-15.9) (maximum score: 21). Data synthesis revealed that older women experienced breast cancer as a journey with challenges during each phase. During diagnosis, they delayed seeking medical help despite symptoms. Age and experience gave them perspective on the impact of their diagnosis. During decision-making, preconceptions and personal values determined choices. In the treatment phase, women experienced medical and social barriers to care. During the post-treatment phase, many experienced treatment adverse effects, but could move on or compartmentalize as coping mechanisms. CONCLUSION: Older women with breast cancer have unique challenges specific to each phase of their treatment journey. Older women may benefit from proactive treatment discussions with health care providers to address their specific needs, individualize care, and assist with cancer care navigation.

Assessing the effect of a hands-on oncoplastic surgery training course: A survey of Canadian surgeons.

BACKGROUND: The adoption of oncoplastic surgery in North America is poor despite evidence supporting the benefits. Surgeons take courses to acquire oncoplastic techniques, however, the effect of these courses is unknown. This study aimed to assess the impact of a hands-on oncoplastic course on surgeons' comfort with oncoplastic techniques and rate of adoption of these techniques in their practice. MATERIAL AND METHODS: An online 10-question survey was developed and distributed to surgeons who had participated in a hands-on oncoplastic course offered in Ontario, Canada. Categorical data were reported using frequencies and percentages. RESULTS: A total of 105 surveys were sent out of which 69 attending surgeons responded (response rate: 65.7%). All respondents stated cosmesis was of the utmost importance in breast conserving surgery. The most common oncoplastic techniques they currently use included glandular re-approximation (98.4%), undermining of skin (93.6%), undermining of the nipple areolar complex (63.4%), and de-epithelialization and repositioning of the nipple areola complex (49.2%). Only 26% of respondnets stated they used more advanced techniques such as mammoplasty. Sixty percent of surgeons reported they used oncoplastic techniques in at least half of their cases. Ninety-two percent of respondents stated that the hands-on course increased the amount of oncoplastic techniques in their practice. At least 70% of respondents stated they would do another hands-on course. The main factor that facilitated the uptake of oncoplastic techniques was a better understanding of surgical techniques and planning. CONCLUSION: A hands-on oncoplastic course helps surgeons adopt oncoplastic surgery techniques into their clinical practice. This teaching model allows surgeons to become comfortable with a variety of techniques. This study supports the relevance of a hands-on oncoplastic course to enhance the availability of safe oncoplastic surgery for breast cancer patients.

Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Regulatory CD4+ T cell (Treg), a subset of tumor-infiltrating lymphocytes (TILs), are known to suppress anticancer immunity but its clinical relevance in human breast cancer remains unclear. In this study, we estimated the relative abundance of Tregs in breast cancer of multiple patient cohorts by using the xCell algorithm on bulk tumor gene expression data. In total, 5177 breast cancer patients from five independent cohorts (TCGA-BRCA, GSE96058, GSE25066, GSE20194, and GSE110590) were analyzed. Treg abundance was not associated with cancer aggressiveness, patient survival, or immune activity markers, but it was lower in metastatic tumors when compared to matched primary tumors. Treg was associated with a high mutation rate of TP53 genes and copy number mutations as well as with increased tumor infiltration of M2 macrophages and decreased infiltration of T helper type 1 (Th1) cells. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) was significantly associated with low Treg abundance in triple negative breast cancer (TNBC) but not in ER-positive/Her2-negative subtype. High Treg abundance was significantly associated with high tumor expression of multiple immune checkpoint inhibitor genes. In conclusion, Treg abundance may have potential as a predictive biomarker of pCR after NAC in TNBC.

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.

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.

Does timing of alloplastic breast reconstruction in older women impact immediate postoperative complications? An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

BACKGROUND: Alloplastic breast reconstruction is safe in well-selected older women. The impact of timing of surgery on complication rates is unknown. This study aimed to determine the immediate (30-day) postoperative complication rates of older women who underwent immediate (IBR) and delayed breast reconstruction (DBR) with alloplastic techniques. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was used to identify women ≥70 years old with in situ or invasive breast cancer who underwent either IBR or DBR (2005-2016). Outcomes included 30-day postoperative morbidity and mortality. RESULTS: A total of 2,085 older women underwent alloplastic breast reconstruction of which 90% and 10% were IBR and DBR, respectively. Both groups had similar median age, body mass index, and frequency of smoking, diabetes mellitus, and steroid use. Tumors were mainly invasive in the IBR group (83.5%) and in situ in the DBR group (83.3%). IBR had significantly longer operative times (median 154 min vs 98 min, p < 0.0001), but equal length of stay (median 3 days vs 3 days, p = 0.1). The 30-day overall morbidity (medical or surgical complication) rate was significantly higher in the IBR group (7.5% vs 1.0%, p < 0.0004). Women with IBR were significantly more likely to develop infectious complications (6% vs 1%, p = 0.002). Cardiac/transfusion, pulmonary, thromboembolic, renal, and neurological morbidity rates were equal between groups. Thirty-day mortality rates were similar across both groups (IBR: 0.05% vs DBR: 0%, p = 0.74). CONCLUSIONS: While overall thirty-day postoperative complication rates in older women who undergo breast reconstruction were low, there were higher rates of infectious complications in the IBR cohort. The risks and benefits of alloplastic breast reconstruction should be discussed with older women undergoing mastectomy for breast cancer treatment.

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.