Association of Medicaid Expansion with Post-mastectomy Reconstruction Rates.

BACKGROUND: The Affordable Care Act sought to improve access to health care for low-income individuals. This study aimed to assess whether expansion of Medicaid coverage increased rates of post-mastectomy reconstruction (PMR) for patients who had Medicaid or no insurance. METHODS: A retrospective analysis performed through the National Cancer Database examined women who underwent PMR and were uninsured or had Medicaid, private insurance, or Medicare, and whose race/ethnicity, age, and state expansion status were known. Trends in the use of PMR after passage of Medicaid expansion in 2014 were evaluated. RESULTS: In all states and at all time periods, patients with private insurance were about twice as likely to undergo PMR as patients who had Medicaid or no insurance. In 2016, only 28.7 % of patients with Medicaid or no insurance in nonexpansion states underwent PMR (p < 0.001) compared with 38.5 % of patients in expansion states (p < 0.001). Patients in expansion states also have higher levels of education, higher income, and greater likelihood of living in metropolitan areas. Additionally, patients in all states saw an increase in early-stage disease, with a concomitant reduction in late disease, but this change was greater in expansion states than in non-expansion states. CONCLUSIONS: Expansion states have larger proportions of patients undergoing PMR than non-expansion states. This difference stems from significant differences in income, education, comorbidities, race, and location. Large metropolitan areas have the largest number of patients undergoing PMR, whereas rural areas have the least.

Exploring the impact of exercise and mind-body prehabilitation interventions on physical and psychological outcomes in women undergoing breast cancer surgery.

PURPOSE: To compare the impact of exercise and mind-body prehabilitation interventions on changes in quality of life and cancer treatment-related symptoms in women with newly diagnosed breast cancer. METHODS: The following describes a secondary analysis of a randomized window of opportunity trial (The Pre-Operative Health and Body Study). Forty-nine women were randomized to participate in either an exercise prehabilitation intervention or a mind-body prehabilitation intervention from the time of enrollment to surgery. Participants (N = 47) completed measures of quality of life, anxiety, depression, and stress at the time of enrollment (T1), post-intervention/surgery (T2), and one-month post-surgery (T3). Changes in outcome measures between groups were compared over time using longitudinal models. RESULTS: Mind-body group participants experienced significant improvements in cognitive functioning in comparison to exercise group participants between T1 and T3 (difference in average change: -9.61, p = 0.04, d = 0.31), otherwise, there were no significant differences between groups. Within group comparisons demonstrated that both groups experienced improvements in anxiety (exercise: average change = -1.18, p = 0.03, d = 0.34; mind-body: average change = -1.69, p = 0.006, d = 0.43) and stress (exercise: average change = -2.33, p = 0.04, d = 0.30; mind-body: average change = -2.59, p = 0.05, d = 0.29), while mind-body group participants experienced improvements in insomnia (average change = -10.03, p = 0.04, d = 0.30) and cognitive functioning (average change = 13.16, p = 0.0003, d = 0.67). CONCLUSIONS: Both prehabilitation interventions impacted cancer treatment-related symptoms. Further work in larger groups of patients is needed to evaluate the efficacy of prehabilitation interventions on quality of life in women with breast cancer. Pre-operative exercise and mind-body interventions may impact physical and/or psychological effects of cancer diagnosis and treatment in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01516190. Registered January 24, 2012.

Omission of Surgical Axillary Lymph Node Staging in Patients with Tubular Breast Cancer.

BACKGROUND: With more effective screening and treatment strategies, there is debate over whether surgical axillary staging should be deescalated for patients with small favorable breast cancers, such as tubular carcinoma (TC). PATIENTS AND METHODS: We identified patients with TC [defined as > 90% tubular tubules (angulated, not multilayered)] and known surgical axillary staging from our institutional database (2000-2018). Using the National Cancer Database (NCDB) (2004-2015), we identified patients with TC, ductal carcinoma in situ (DCIS), and pT1 estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). We determined the rates of lymph node (LN) metastases, and the 5- and 10-year overall survival (OS) for patients with LN-negative versus LN-positive disease using the Kaplan-Meier method and propensity match analysis. RESULTS: In our institutional cohort, we identified 112 patients with T1 TC; only one (0.9%) patient had nodal involvement. In the NCDB cohort, we identified 6938 patients with T1 TC; 323 (4.7%) patients had axillary LN disease. The rate of axillary LN involvement for TC was comparable to that identified for patients with DCIS (4.2%), and much lower than that found for patients with grade I-III, T1, ER-positive IDC (20.5%), and patients with grade I, T1, ER-positive IDC (14.4%). There was no difference in 5-year (94.6% versus 95.4%, p = 0.67) and 10-year (83.9% versus 85.2%, p = 0.98) OS between TC patients with or without LN involvement. Kaplan-Meier survival curves even after propensity score matching suggest that tubular histology is independently associated with improved survival. CONCLUSIONS: T1 TC is an excellent starting point for deescalation of surgical axillary staging.

Cancer Awareness and Stigma in Rural Assam India: Baseline Survey of the Detect Early and Save Her/Him (DESH) Program.

BACKGROUND: India has an estimated incidence of more than one million cancers annually. Breast, oral, and cervical cancers account for over one-third of newly diagnosed cases. With the introduction of pilot cancer screening programs in India, little is known about current sociocultural barriers that may hinder acceptance of screening and treatment. We sought to identify knowledge gaps, misconceptions, and stigmas surrounding cancer diagnosis. PATIENTS AND METHODS: A baseline survey was conducted in Assam, India, as part of the Detect Early and Save Her/Him program, a mobile screening program for breast, oral, and cervical cancer. Data were collected on participants' cancer knowledge, and attitudes towards screening, diagnosis, and treatment. RESULTS: Of the 923 residents who participated, a large majority (92.9%; n = 858) were neither aware of cancer screening availability nor had prior screening. Low-medium awareness was demonstrated regarding the carcinogenic effects of betel nuts (n = 433, 47%). Only one-third of participants recognized oral ulcers and dysphagia as cancer symptoms. Approximately 10% of respondents had misconceptions about cancer etiologies, and 42-57% endorsed statements reflecting a negative stigma towards cancer, including its long-term detrimental effects on personal, occupational, and familial life. However, the majority (68-96%) agreed with statements endorsing positive community support and medical care for cancer patients. CONCLUSIONS: This study identifies actionable targets for intervention in cancer education and awareness within a large rural Indian population. Education to address preventable causes of cancer and to correct misconceptions and stigma is a critical component in ensuring the successful implementation of cancer screening programs.

Prediction of Persistent Pain Severity and Impact 12 Months After Breast Surgery Using Comprehensive Preoperative Assessment of Biopsychosocial Pain Modulators.

BACKGROUND: Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence. METHODS: This prospective longitudinal observational cohort study used detailed and comprehensive psychosocial and psychophysical assessment to characterize individual pain-processing phenotypes in 259 women preoperatively. Pain severity and functional impact then were longitudinally assessed using both validated surgery-specific and general pain questionnaires to survey patients who underwent lumpectomy, mastectomy, or mastectomy with reconstruction in the first postsurgical year. An agnostic, multivariable modeling strategy identified consistent predictors of several pain outcomes at 12 months. RESULTS: The preoperative characteristics most consistently associated with PPMP outcomes were preexisting surgical area pain, less education, increased somatization, and baseline sleep disturbance, with axillary dissection emerging as the only consistent surgical variable to predict worse pain. Greater pain catastrophizing, negative affect, younger age, higher body mass index (BMI), and chemotherapy also were independently predictive of pain impact, but not severity. Sensory disturbance in the surgical area was predicted by a slightly different subset of factors, including higher preoperative temporal summation of pain. CONCLUSIONS: This comprehensive approach assessing consistent predictors of pain severity, functional impact, and sensory disturbance may inform personalized prevention of PPMP and also may allow stratification and enrichment in future preventive studies of women at higher risk of this outcome, including pharmacologic and behavioral interventions and regional anesthesia.

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance).

BACKGROUND: De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively. PATIENTS AND METHODS: A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status. RESULTS: In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001). CONCLUSIONS: Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials.

Apocrine Breast Cancer: Unique Features of a Predominantly Triple-Negative Breast Cancer.

INTRODUCTION: Invasive apocrine carcinoma is a rare breast cancer that is frequently triple negative. Little is known about the characteristics of its molecular subtypes. We compared the incidence, demographics, and clinicopathologic features of this cancer with non-apocrine carcinomas stratified by molecular subtype. METHODS: Women with invasive apocrine cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic and demographic features were compared with non-apocrine carcinomas, both overall using data from 2004 to 2017 and stratified by molecular subtypes using data from 2010 to 2017. The life table method was used to determine the 7-year breast cancer-specific survival. RESULTS: Compared with non-apocrine cancers, apocrine cancers presented at a younger age, with larger, higher-grade tumors that were much more likely to be triple negative (50% vs. 11%) or human epidermal growth factor receptor 2 (HER2)-positive (28% vs. 15%) and less likely to be luminal (22% vs. 74%); however, the 7-year survival was the same at 85%. The characteristics varied dramatically by molecular type. Compared with non-apocrine triple-negative, apocrine triple-negative patients were less likely to be African American and were much older, with smaller, lower-grade tumors and much better survival (86% vs. 74%). In contrast, compared with luminal non-apocrine, apocrine luminal patients had larger, higher-grade tumors and worse survival (79% vs. 89%). CONCLUSIONS: Invasive apocrine carcinomas have more aggressive features than non-apocrine carcinomas but the breast cancer-specific survival is the same. Half of these apocrine tumors are triple negative but these have more favorable features and much better survival than non-apocrine triple-negative cancers.

Optimal Management for Residual Disease Following Neoadjuvant Systemic Therapy.

OPINION STATEMENT: Treatment sequencing in early-stage breast cancer has significantly evolved in recent years, particularly in the triple negative (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive subsets. Instead of surgery first followed by chemotherapy, several clinical trials showed benefits to administering systemic chemotherapy (and HER2-targeted therapies) prior to surgery. These benefits include more accurate prognostic estimates based on the extent of residual cancer that can also guide adjuvant treatment, and frequent tumor downstaging that can lead to smaller surgeries in patients with large tumors at diagnosis. Patients with extensive invasive residual cancer after neoadjuvant therapy are at high risk for disease recurrence, and two pivotal clinical trials, CREATE-X and KATHERINE, demonstrated improved recurrence free survival with adjuvant capecitabine and ado-trastuzumab-emtansine (T-DM1) in TNBC and HER2-positive residual cancers, respectively. Patients who achieve pathologic complete response (pCR) have excellent long-term disease-free survival regardless of what chemotherapy regimen induced this favorable response. This allows escalation or de-escalation of adjuvant therapy: patients who achieved pCR could be spared further chemotherapy, while those with residual cancer could receive additional chemotherapy postoperatively. Ongoing clinical trials are testing this strategy (CompassHER2-pCR: NCT04266249). pCR also provides an opportunity to assess de-escalation of locoregional therapies. Currently, for patients with residual disease in the lymph nodes (ypN+), radiation therapy entails coverage of the undissected axilla, and may include supra/infraclavicular/internal mammary nodes in addition to the whole breast or chest wall, depending on the type of surgery. Ongoing trials are testing the safety of omitting post-mastectomy breast and post-lumpectomy nodal irradiation (NCT01872975) as well as omitting axillary lymph node dissection (NCT01901094) in the setting of pCR. Additionally, evolving technologies such as minimal residual disease (MRD) monitoring in the blood during follow-up may allow early intervention with "second-line systemic adjuvant therapy" for patients with molecular relapse which might prevent impending clinical relapse.

Surgical Oncologists and the COVID-19 Pandemic: Guiding Cancer Patients Effectively through Turbulence and Change.

BACKGROUND: The COVID-19 pandemic has posed extraordinary demands from patients, providers, and health care systems. Despite this, surgical oncologists must maintain focus on providing high-quality, empathetic care for the almost 2 million patients nationally who will be diagnosed with operable cancer this year. The focus of hospitals is transitioning from initial COVID-19 preparedness activities to a more sustained approach to cancer care. METHODS: Editorial Board members provided observations of the implications of the pandemic on providing care to surgical oncology patients. RESULTS: Strategies are presented that have allowed institutions to successfully prepare for cancer care during COVID-19, as well as other strategies that will help hospitals and surgical oncologists manage anticipated challenges in the near term. Perspectives are provided on: (1) maintaining a safe environment for surgical oncology care; (2) redirecting the multidisciplinary model to guide surgical decisions; (3) harnessing telemedicine to accommodate requisite physical distancing; (4) understanding interactions between SARS CoV-2 and cancer therapy; (5) considering the ethical impact of professional guidelines for surgery prioritization; and (6) advocating for our patients who require oncologic surgery in the midst of the COVID-19 pandemic. CONCLUSIONS: Until an effective vaccine becomes available for widespread use, it is imperative that surgical oncologists remain focused on providing optimal care for our cancer patients while managing the demands that the COVID-19 pandemic will continue to impose on all of us.

Bilateral mastectomy operations and the role for the cosurgeon technique: A Nationwide analysis of surgical practice patterns.

Traditionally, bilateral mastectomy (BM) operations are performed by a single surgeon but a two-attending co-surgeon technique (CST) has been described. A questionnaire was sent to members of the American Society of Breast Surgeons to assess national BM practices and analyze utilization and perceived benefits of the CST. Among surgeons responding, most continue to use the single-surgeon approach for BMs; however, 14.1% utilize the CST and up to 31% are interested in future CST use. Time savings, mentorship, cost savings, and opportunity to learn new techniques were identified as perceived CST advantages.

Impact of Genomic Assay Testing and Clinical Factors on Chemotherapy Use After Implementation of Standardized Testing Criteria.

BACKGROUND: For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention. MATERIALS AND METHODS: We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing. RESULTS: The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt. CONCLUSION: Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation. IMPLICATIONS FOR PRACTICE: This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays.

National trends of synchronous bilateral breast cancer incidence in the United States.

PURPOSE: Increase in breast cancer survivorship, advancements in diagnostic imaging and standardization of contralateral breast screening before breast cancer surgery have resulted in increased detection of contralateral breast cancer (CBC). The aim of this study was to assess national trends of synchronous bilateral breast cancer (sBBC) and metachronous bilateral breast cancer (mBBC) incidence in newly diagnosed breast cancer patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1973-2014) was used to identify 11,177 women diagnosed with CBC. CBC was classified as sBBC when primary breast cancer in both breasts is diagnosed in the same year, or as mBBC, when diagnosed more than one year from primary breast cancer. Temporal trends in sBBC incidence were then evaluated using the Cochran-Armitage test for trend. RESULTS: Of the 11,177 women diagnosed with CBC, 4228 (38%) had sBBC and 6949 (62%) had mBBC. The incidence of sBBC increased significantly from 1.4% in 1975 to 2.9% in 2014 (p < 0.001). sBBC was more likely to be diagnosed as early stage in recent years (78% in 1975 vs. 90% in 2014 [p < 0.001]), and 69% of patients were treated with mastectomy in 2014. CONCLUSION: The number of sBBC has increased, and contralateral tumors are more likely to be detected at an early stage with the first primary breast cancer. Despite the early stage findings, most were treated with mastectomy. Further studies are needed to define the best therapy for patients with contralateral disease and optimal surveillance and detection methods.

Long-term outcomes of breast-conserving therapy for women with ductal carcinoma in situ.

PURPOSE: Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT). METHODS: We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events. RESULTS: At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05). CONCLUSIONS: With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.

Survival Outcomes for Patients With Clinical Complete Response After Neoadjuvant Chemotherapy: Is Omitting Surgery an Option?

BACKGROUND: Surgery after neoadjuvant chemotherapy (NCT) is an accepted treatment approach for locally advanced and some early-stage breast cancers, even for patients with a clinical complete response (cCR) after NCT. This study sought to evaluate the survival outcomes for patients with cCR to NCT who did not undergo surgery. METHODS: The National Cancer Data Base (NCDB) was used to identify 93,417 women age 18 years or older with a diagnosis of invasive breast cancer who received NCT between 2010 and 2015. The study identified 350 women with cT1-4, N0-3, and M0 tumors who underwent NCT and did not have surgery. A matched surgical cohort was extracted from the NCDB, and overall survival (OS) was compared between the surgical and nonsurgical patients after NCT. RESULTS: Of the 350 NCT patients who did not undergo surgery, 45 (12.9%) had cCR, 51 (14.6%) had a partial response, 241 (68.9%) had a response but whether complete or partial was not recorded, and 13 (3.7%) had no response/progression. The 5-year OS was better in the cCR group than in the no-cCR group (96.8% vs 69.8%; p = 0.004). A 5-year OS analysis of the cCR patients without surgery (n = 45; median follow-up period, 37 months) compared with the patients with a pathologic complete response who underwent surgery (n = 3938; median follow-up period, 43 months) showed no statistically significant difference (96.8% vs 92.5%, respectively; p = 0.15). CONCLUSION: This retrospective cohort study demonstrated that active surveillance or de-escalation therapy may be an option for patients who achieve cCR. Prospective studies are underway to determine whether a subgroup of patients may forgo surgery in the setting of cCR after NCT.

National Patterns of Breast Reconstruction and Nipple-Sparing Mastectomy for Breast Cancer, 2005-2015.

BACKGROUND: The purpose of this study was to explore national patterns in the uptake of breast reconstruction and nipple-sparing mastectomy (NSM). METHODS: We used the National Cancer Database to identify all women who underwent mastectomy for stage 0-III breast cancer between 2005-2015. Multivariable logistic regression was used to determine factors associated with receipt of reconstruction, with subset analyses performed to determine trends and predictors of NSM in those who underwent mastectomy with reconstruction. RESULTS: Our cohort consisted of 395,815 women, 238,568 (60.3%) who underwent mastectomy alone and 157,247 (39.7%) who underwent mastectomy followed by reconstruction. The use of breast reconstruction increased from 22.3% of mastectomy cases in 2005 to 49.7% of mastectomy cases in 2015 (odds ratio [OR] 9.7, 95% confidence interval [CI] 7.3-12.8). Among those receiving reconstruction, the use of NSM increased from 1.7% in 2005 to 14.3% in 2015 (OR 9.4, 95% CI 7.1-12.5), with increased utilization among those with early-stage and locally advanced disease, such that by 2015, NSM was performed in 15.3% of mastectomies with reconstruction for DCIS, 14.3% of mastectomies with reconstruction for stage I-II breast cancer, and 10.7% of mastectomies with reconstruction for stage III breast cancer. Factors strongly predicting receipt of NSM included age < 45 years, smaller clinical tumor size, clinically node negative disease, use of neoadjuvant therapy, and facility type. CONCLUSIONS: There has been a dramatic increase in the use of breast reconstruction and NSM between 2005-2015. Further prospective studies evaluating oncologic outcomes of NSM in locally advanced breast cancer are warranted.

Surgical Management of the Axilla in Clinically Node-Positive Patients Receiving Neoadjuvant Chemotherapy: A National Cancer Database Analysis.

BACKGROUND: The feasibility of sentinel lymph node biopsy (SLNB) in patients with clinically node-positive (cN+) disease who convert to clinically node-negative (cN0) disease following neoadjuvant chemotherapy (NAC) has been evaluated in several large clinical trials, but it remains unclear whether the approach has been broadly adopted in the United States. METHODS: The National Cancer Database was used to identify women diagnosed with cN+ breast cancer who received NAC followed by surgery between 2012 and 2015. Trends in axillary surgery were evaluated and multivariable logistic regression analyses performed to determine factors associated with receipt of SLNB. RESULTS: Of 12,965 women cN+ at baseline, the use of SLNB increased from 31.8% in 2012 to 49% in 2015 (p < 0.001). Using axillary pCR as a surrogate for patients who convert to cN0 following NAC, among 5127 (39.5%) ypN0 patients, SLNB increased from 38.2 to 58.4% over the study period (p < 0.001), resulting in avoidance of axillary dissection in 42.2% of ypN0 patients by 2015. In adjusted analyses, factors significantly associated with SLNB attempt included cN1 disease, age < 45 years, treatment facility type, triple-negative and HER2-positive subtypes, and year of diagnosis. In women with residual isolated tumor cells (ITCs), micrometastases, and ypN1 disease, SLNB was the only axillary procedure performed in 36.9%, 23.6%, and 13.0% of cases. CONCLUSIONS: The use of SLNB in cN+ patients receiving NAC increased significantly between 2012 and 2015. SLNB alone was performed in more than 10% of patients with ypN1 disease, 20% with micrometastases, and 35% with ITCs; the oncologic safety of omitting axillary dissection in these patients requires further evaluation.

Patterns of Axillary Management in Stages 2 and 3 Hormone Receptor-Positive Breast Cancer by Initial Treatment Approach.

BACKGROUND: Data regarding axillary management after neoadjuvant endocrine therapy (NET) are lacking. This study examined axillary management of hormone receptor-positive (HR+) patients based on initial treatment with NET, neoadjuvant chemotherapy (NAC), or upfront surgery. METHODS: Patients with stage 2 or 3 HR+/HER2- breast cancer treated between 2012 and 2015 were identified in the National Cancer Database. The study examined axillary surgery [sentinel lymph node biopsy (SLNB), SLNB followed by axillary lymph node dissection (ALND), or upfront ALND] by initial treatment stratified by cN0/N1 using pairwise comparisons and multivariable logistic regression. RESULTS: Of 92,204 eligible patients, 2138 (2.3%) received NET, 11,014 (12%) received NAC, and 79,052 (85.7%) received surgery. Among 60,998 cN0 patients, attempted SLNB was more likely for surgery patients (86.2%, 47,159/54,684) and NET patients (85.8%, 1342/1564) than for NAC patients (79.9%, 3793/4750) (both p < 0.001). Among 31,206 cN1 patients, attempted SLNB was more likely for the surgery patients (46.0%, 11,201/24,368) than for the NET patients (41.8%, 240/574; p = 0.05) or the NAC patients (39.8%, 2491/6264; p < 0.0001). The differences between surgery and NET did not persist in the adjusted analyses. Among both the cN0 patients (n = 13,856) and the cN1 patients (n = 8688) with pN1 disease shown by SLNB, the NET patients were treated with ALND less frequently than those receiving NAC or surgery (p < 0.0001 for all comparisons). In the multivariate analysis, for the patients with pN1 disease shown by SLNB, NET use was associated with increased odds of undergoing SLNB alone [cN0 patients: odds ratio (OR), 1.31, 95% confidence interval (CI), 1.04-1.64; cN1 patients: OR 1.45; 95% CI 1.00-2.10]. CONCLUSIONS: For stages 2 and 3 HR+/HER2- patients, SLNB use after NET was similar to that for upfront surgery. Among those with pN1 disease, the NET patients were less likely to undergo ALND. Additional outcomes data are needed to guide axillary management after NET.

Prognostic Significance of Residual Axillary Nodal Micrometastases and Isolated Tumor Cells After Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: The prognostic significance of low-volume residual nodal disease following neoadjuvant chemotherapy (NAC) is unknown. METHODS: Women with cT1-4N0-1 breast cancer treated with NAC were identified from Dana-Farber/Brigham and Women's Cancer Center (DFBWCC) and the National Cancer Database (NCDB). Disease-free survival (DFS) and overall survival (OS) estimates according to pathologic nodal status were calculated using the Kaplan-Meier method, with Cox proportional hazards regression used to assess the effect of clinical variables on survival outcomes. RESULTS: Among 967 DFBWCC patients, 27 (2.8%) had residual isolated tumor cells (ITCs) and 61 (6.3%) had micrometastases. Five-year DFS was significantly worse in those with residual ITCs (73.5%) and micrometastases (74.7%) relative to those who were ypN0 following NAC (88.4%, p < 0.001). On adjusted analysis, those with residual ITCs (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.20-3.81) and micrometastases (HR 2.14, 95% CI 1.20-3.81) had increased risk of recurrence relative to ypN0 patients. Among 35,536 NCDB patients, 543 (1.5%) had ITCs and 1132 (3.2%) had micrometastases. Five-year OS estimates were significantly worse with increasing residual nodal burden: ypN0, 88.9%; ypN0[i+], 82.8%; ypN1mi, 79.5%; ypN1, 77.6% (p < 0.001). Compared with patients with ypN0 disease, NCDB patients with ITCs and micrometastases had 1.9- and 2.2-fold risk of death (p < 0.001). On subgroup analysis, the effect of low-volume residual disease on mortality was most pronounced in patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive disease. CONCLUSIONS: Low-volume residual nodal disease following NAC is associated with poorer DFS and OS relative to those who are node negative.

Benefit of regional anaesthesia on postoperative pain following mastectomy: the influence of catastrophising.

BACKGROUND: Previous studies suggest that truncal regional anaesthesia (TRA), including techniques such as paravertebral block, may contribute significantly to analgesia after mastectomy. However, the severity and impact of postoperative pain varies markedly amongst individuals, making the identification of patients who would benefit most from TRA a potentially important step toward personalised perioperative care. METHODS: In this prospective observational study, mastectomy patients (n=122) were recruited and systematically assessed for psychosocial characteristics including pain catastrophising before surgery, and either received preoperative TRA (n=57) or no block (n=65). RESULTS: Age, baseline pain, and psychosocial traits did not differ between these groups. TRA was associated with lower overall pain scores and opioid consumption perioperatively, with a larger proportion of patients without block (50% vs 28%) reporting moderate-severe pain (more than three/10) on the day of surgery. Mixed model analysis of variance revealed a significant interaction between catastrophising and TRA, such that amongst patients with high baseline catastrophising, TRA was associated with substantially lower pain severity score (58% lower), while amongst patients with low baseline catastrophising, TRA was associated with only 18% lower pain severity. At 2 weeks, this interaction between baseline catastrophising and TRA was also observed when examining surgical pain burden, with higher baseline catastrophising patients who had received TRA reporting lower pain and less frequent opioid use (40% vs 70% of patients). CONCLUSIONS: TRA provided immediate analgesic benefit for patients undergoing mastectomy on the day of surgery, but this effect appeared more pronounced and sustained amongst patients with higher baseline catastrophising. CLINICAL TRIAL REGISTRATION: NCT02329574.

Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial.

BACKGROUND: Although several randomised trials in patients with triple-negative breast cancer have shown that the addition of carboplatin, with or without poly(ADP-ribose) polymerase (PARP) inhibitors, to neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response, the use of these therapies in this setting has remained controversial. The BrighTNess trial was designed to assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled trial (BrighTNess) across 145 sites in 15 countries. Patients aged 18 years and older with previously untreated histologically or cytologically confirmed clinical stage II-III triple-negative breast cancer, who were candidates for potentially curative surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned (2:1:1) by an interactive response technology system via permuted blocks (block size of four) within strata to receive one of three segment 1 regimens: paclitaxel (80 mg/m2 intravenously weekly for 12 doses) plus carboplatin (area under the curve 6 mg/mL per min, intravenously every 3 weeks, for four cycles) plus veliparib (50 mg orally, twice a day); paclitaxel plus carboplatin plus veliparib placebo (twice a day); or paclitaxel plus carboplatin placebo (every 3 weeks for four cycles) plus veliparib placebo. Following segment 1, all patients were assigned to segment 2 in which they received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. Randomisation for segment 1 was stratified by germline BRCA mutation status, nodal stage, and planned schedule of doxorubicin and cyclophosphamide administration. The primary endpoint was pathological complete response in breast and lymph nodes as determined by site pathologists following completion of neoadjuvant therapy. Efficacy analyses were done by intention to treat and safety analyses included all patients who received at least one dose of study treatment. These are the first results of an ongoing clinical trial; the data cutoff for the analyses presented was Dec 8, 2016. This study is registered with ClinicalTrials.gov, number NCT02032277. FINDINGS: Between April 4, 2014, and March 18, 2016, 634 patients were randomly assigned: 316 to paclitaxel plus carboplatin plus veliparib, 160 to paclitaxel plus carboplatin, and 158 to paclitaxel alone. The proportion of patients who achieved a pathological complete response was higher in the paclitaxel, carboplatin, and veliparib group than in patients receiving paclitaxel alone (168 [53%] of 316 patients vs 49 [31%] of 158, p<0·0001), but not compared with patients receiving paclitaxel plus carboplatin (92 [58%] of 160 patients, p=0·36). Grade 3 or 4 toxicities, and serious adverse events were more common in patients receiving carboplatin, whereas veliparib did not substantially increase toxicity. The most common grade 3 or 4 events overall were neutropenia (352 [56%] of 628 patients), anaemia (180 [29%]), and thrombocytopenia (75 [12%]) through complete treatment, and febrile neutropenia (88 [15%] of 601 patients) during segment 2. The most common serious adverse events were febrile neutropenia (80 [13%] of 628 patients) and anaemia (20 [3%]). INTERPRETATION: Although the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the proportion of patients with triple-negative breast cancer who achieved a pathological complete response, the addition of veliparib to carboplatin and paclitaxel did not. Increased toxicities with the addition of carboplatin (with or without veliparib) to paclitaxel were manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and cyclophosphamide. Given the consistent results with previous studies, the addition of carboplatin appears to have a favourable risk to benefit profile and might be considered as a potential component of neoadjuvant chemotherapy for patients with high-risk, triple-negative breast cancer. FUNDING: AbbVie.