Breast surgery after neoadjuvant systemic therapy.

For patients with operable breast cancer, neoadjuvant systemic therapy (NST) can be used to downstage the primary tumor in the breast and to facilitate breast-conserving surgery (BCS) in patients with large tumors who desire breast conservation. Rates of breast pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) are highest in patients with triple-negative and human epidermal growth factor receptor 2 (HER2) positive (HER2+) disease; however, achieving pCR is not necessary for successful downstaging and avoidance of mastectomy, and rates of conversion to BCS-eligibility are high across all receptor subtypes. Neoadjuvant endocrine therapy (NET) can be used instead of NAC in postmenopausal patients with hormone receptor positive (HR+)/HER2 negative (HER2-) breast cancer to downstage the breast, particularly when the patient has no clear indication for systemic chemotherapy, but desires breast conservation. In patients treated with NET, rates of conversion to BCS-eligibility are similar to rates observed with NAC. The oncologic safety of BCS after NAC and NET has been established in prospective trials, and local recurrence (LR) rates are acceptably low provided negative surgical margins can be obtained. Investigation is under way to determine the feasibility and safety of omitting breast surgery in patients with responsive subtypes who have no residual invasive or in situ disease identified on post-treatment tumor bed biopsies; however, the significant risk of missing residual disease-which may impact selection of adjuvant systemic therapy-may preclude future adoption of this approach.

Timing of Chemotherapy and Patient-Reported Outcomes After Breast-Conserving Surgery and Mastectomy with Immediate Reconstruction.

INTRODUCTION: Receipt of chemotherapy is associated with decreased satisfaction after breast surgery, but whether timing as adjuvant versus neoadjuvant (NAC) affects patient-reported outcomes (PROs) is unclear. We examined associations between chemotherapy timing and PROs after breast-conserving surgery (BCS) and mastectomy with immediate reconstruction (M-IR). METHODS: In this retrospective cohort study of patients with stage I-III breast cancer undergoing chemotherapy between January 2017 and December 2019, we compared satisfaction with breasts (SABTR) and chest physical well-being (PWB-CHEST) between chemotherapy groups in BCS and M-IR cohorts. Median SABTR and PWB-CHEST scores (scale 0-100) were compared between chemotherapy groups at baseline and for 3 years postoperatively. Factors associated with SABTR and PWB-CHEST at 1 and 2 years were assessed with multivariable linear regression. RESULTS: Overall, 640 patients had BCS and 602 had M-IR; 210 (33%) BCS patients and 294 (49%) M-IR patients had NAC. Following BCS, SABTR was higher than baseline at all postoperative timepoints, whereas 3-year SABTR remained similar to baseline following M-IR, independent of chemotherapy timing. In both surgical cohorts, PWB-CHEST was lowest after NAC at 6 months compared with baseline but was similar to adjuvant counterparts by 3 years. NAC was not a statistically significant predictor of SABTR or PWB-CHEST in either surgical cohort on multivariable analysis. CONCLUSIONS: For patients with breast cancer who require chemotherapy, neoadjuvant versus adjuvant timing does not impact long-term PROs in this study. These findings may inform shared decision making regarding the sequence of treatment in patients with operable disease.

Arterial-colonic fistula secondary to colonic stent erosion into the left external iliac artery.

Self-expandable metal stent (SEMS) are widely utilized as a bridge to surgical intervention and for palliative treatment of malignant bowel obstructions. The risk of complications associated with SEMS is low in well-selected patients. Stent erosion is a rare but serious adverse event that is associated with high morbidity and mortality. Here, we report the case of a 74-year-old patient with a colonic obstruction secondary to a pelvic mass that was treated with SEMS and radiotherapy, who developed a partial thickness stent erosion and recurrent hematochezia 6 years after placement. Endoscopic retrieval was not technically feasible. During attempted surgical resection, massive hemorrhage occurred from a colonic-arterial fistula to the left external iliac artery resulting in death. While SEMS remain an effective, minimally invasive approach for the management of bowel obstructions, prolonged in-situ lifetime may confer an increased risk of serious adverse events including erosion and fistula formation.

ASO Visual Abstract: Patient-Reported Outcome Measures in Patients with Clinical T4 Breast Cancer Treated with Mastectomy With and Without Reconstruction.

AIM: Do patient-reported outcome measures differ among clinical T4 patients undergoing mastectomy with and without reconstruction? FINDINGS: Neither reconstruction nor timing of reconstruction were associated with superior outcomes for breast satisfaction, physical well-being of the chest, or psychosocial well-being at any timepoint.

Patient-Reported Outcome Measures for Patients Who Have Clinical T4 Breast Cancer Treated via Mastectomy with and Without Reconstruction.

BACKGROUND: Patients with clinical T4M0 breast cancer are recommended to undergo neoadjuvant chemotherapy, modified radical mastectomy, and postmastectomy radiotherapy. This study determined whether BREAST-Q scores differ by decision to pursue reconstruction or timing of reconstruction. METHODS: This retrospective, single-institutional study analyzed cT4 breast cancer patients from 2014 to 2021 without evidence of distant metastatic disease undergoing mastectomy with or without reconstruction. As routine care, BREAST-Q was administered preoperatively, then 6 months, 1 year, and 2 years postoperatively. Satisfaction and quality-of-life domains were compared between mastectomy with no reconstruction (NR), immediate reconstruction (IR), and delayed reconstruction (DR) groups. RESULTS: Of the 144 patients eligible for this study, 71 (49%) had NR, 36 (25%) had DR, and 37 (26%) had IR. The patients undergoing reconstruction were younger and more likely to elect contralateral prophylactic mastectomy. Timing of reconstruction was not associated with significant differences in satisfaction with breasts (SATBR) at any time point. For the patients who had DR, breast satisfaction increased over time after reconstructive surgery. Physical well-being of the chest (PWB-CHEST) did not significantly differ among IR, DR, and NR at any time point. The patients who underwent DR experienced improvement in PWB-CHEST scores from preoperative scores. The patients with IR and NR experienced PWB-CHEST decline over time. Psychosocial well-being (PSWB) did not differ significantly across time or by subgroup. CONCLUSIONS: The patients with T4 breast cancer who elected reconstruction did not differ in patient-reported outcomes based on timing of reconstruction. In the DR cohort, SATBR significantly improved after reconstructive surgery. These data can help inform breast reconstructive decision-making for patients facing the choice among DR, IR, and NR.

Use of a supervised machine learning model to predict Oncotype DX risk category in node-positive patients older than 50 years of age.

PURPOSE: The use of the Oncotype DX recurrence score (RS) to predict chemotherapy benefit in patients with hormone receptor-positive/HER2 negative (HR+/HER2-) breast cancer has recently expanded to include postmenopausal patients with N1 disease. RS availability is limited in resource-poor settings, however, prompting the development of statistical models that predict RS using clinicopathologic features. We sought to assess the performance of our supervised machine learning model in a cohort of patients > 50 years of age with N1 disease. METHODS: We identified patients > 50 years of age with pT1-2N1 HR+/HER2- breast cancer and applied the statistical model previously developed in a node-negative cohort, which uses age, pathologic tumor size, histology, progesterone receptor expression, lymphovascular invasion, and tumor grade to predict RS. We measured the model's ability to predict RS risk category (low: RS ≤ 25; high: RS > 25). RESULTS: Our cohort included 401 patients, 60.6% of whom had macrometastases, with a median of 1 positive node. The majority of patients had a low-risk observed RS (85.8%). For predicting RS category, the model had specificity of 97.3%, sensitivity of 31.8%, a negative predictive value of 87.9%, and a positive predictive value of 70.0%. CONCLUSION: Our model, developed in a cohort of node-negative patients, was highly specific for identifying cN1 patients > 50 years of age with a low RS who could safely avoid chemotherapy. The use of this model for identifying patients in whom genomic testing is unnecessary would help decrease the cost burden in resource-poor settings as reliance on RS for adjuvant treatment recommendations increases.

How Much Pain Will I Have After Surgery? A Preoperative Nomogram to Predict Acute Pain Following Mastectomy.

INTRODUCTION: Acute postoperative pain affects time to opioid cessation and quality of life, and is associated with chronic pain. Effective screening tools are needed to identify patients at increased risk of experiencing more severe acute postoperative pain, and who may benefit from multimodal analgesia and early pain management referral. In this study, we develop a nomogram to preoperatively identify patients at high risk of moderate-severe pain following mastectomy. METHODS: Demographic, psychosocial, and clinical variables were retrospectively assessed in 1195 consecutive patients who underwent mastectomy from January 2019 to December 2020 and had pain scores available from a post-discharge questionnaire. We examined pain severity on postoperative days 1-5, with moderate-severe pain as the outcome of interest. Multivariable logistic regression was performed to identify variables associated with moderate-severe pain in a training cohort of 956 patients. The final model was determined using the Akaike information criterion. A nomogram was constructed using this model, which also included a priori selected clinically relevant variables. Internal validation was performed in the remaining cohort of 239 patients. RESULTS: In the training cohort, 297 patients reported no-mild pain and 659 reported moderate-severe pain. High body mass index (p = 0.042), preoperative Distress Thermometer score ≥4 (p = 0.012), and bilateral surgery (p = 0.003) predicted moderate-severe pain. The resulting nomogram accurately predicted moderate-severe pain in the validation cohort (AUC =  0.735). CONCLUSIONS: This nomogram incorporates eight preoperative variables to provide a risk estimate of acute moderate-severe pain following mastectomy. Preoperative risk stratification can identify patients who may benefit from individually tailored perioperative pain management strategies and early postoperative interventions to treat pain and assist with opioid tapering.

The Effect of Age on Outcomes After Neoadjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Younger women (age ≤ 40 years) with breast cancer undergoing neoadjuvant chemotherapy (NAC) have higher rates of pathologic complete response (pCR); however, it is unknown whether axillary or breast downstaging rates differ by age. In this study, we compared pCR incidence and surgical downstaging rates of the breast and axilla post NAC, between patients aged ≤ 40, 41-60, and ≥ 61 years. METHODS: We identified 1383 women with stage I-III breast cancer treated with NAC and subsequent surgery from November 2013 to December 2018. pCR and breast/axillary downstaging rates were assessed and compared across age groups. RESULTS: Younger women were significantly more likely to have ductal histology, poorly differentiated tumors, and BRCA mutations; 35% of tumors were hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 36% were HER2-positive (HER2+), and 29% were triple negative (TN), with similar subtype distribution across age groups (p = 0.6). Overall, pCR rates did not differ by age, however among patients with TN tumors (n = 394), younger women had higher pCR rates (52% vs. 35% among those aged 41-60 years and 29% among those aged ≥61 years; p = 0.007) and were more likely to have tumors with high tumor-infiltrating lymphocyte (TIL) concentrations (p < 0.001). Downstaging to breast-conserving surgery (BCS) eligibility post NAC among initially BCS-ineligible patients was similar across age groups; younger women chose BCS less often (p < 0.001). Among cN1 patients (n = 813), 52% of women ≤40 years of age avoided axillary lymph node dissection (ALND) with NAC, versus 39% and 37% in the older groups (p < 0.001). CONCLUSIONS: Younger women undergoing NAC for axillary downstaging were more likely to avoid ALND across all subtypes; however, overall pCR rates did not differ by age. Despite equivalent breast downstaging and BCS eligibility rates across age groups, younger women were less likely to undergo BCS.

Supervised machine learning model to predict oncotype DX risk category in patients over age 50.

PURPOSE: Routine use of the oncotype DX recurrence score (RS) in patients with early-stage, estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer is limited internationally by cost and availability. We created a supervised machine learning model using clinicopathologic variables to predict RS risk category in patients aged over 50 years. METHODS: From January 2012 to December 2018, we identified patients aged over 50 years with T1-2, ER+/HER2-, node-negative tumors. Clinicopathologic data and RS results were randomly split into training and validation cohorts. A random forest model with 500 trees was developed on the training cohort, using age, pathologic tumor size, histology, progesterone receptor (PR) expression, lymphovascular invasion (LVI), and grade as predictors. We predicted risk category (low: RS ≤ 25, high: RS > 25) using the validation cohort. RESULTS: Of the 3880 tumors identified, 1293 tumors comprised the validation cohort in patients of median (IQR) age 62 years (56-68) with median (IQR) tumor size 1.2 cm (0.8-1.7). Most tumors were invasive ductal (80.3%) of low-intermediate grade (80.5%) without LVI (80.9%). PR expression was ≤ 20% in 27.3% of tumors. Specificity for identifying RS ≤ 25 was 96.3% (95% CI 95.0-97.4) and the negative predictive value was 92.9% (95% CI 91.2-94.4). Sensitivity and positive predictive value for predicting RS > 25 was lower (48.3 and 65.1%, respectively). CONCLUSION: Our model was highly specific for identifying eligible patients aged over 50 years for whom chemotherapy can be omitted. Following external validation, it may be used to triage patients for RS testing, if predicted to be high risk, in resource-limited settings.

Association Between Local Anesthetic Dosing, Postoperative Opioid Requirement, and Pain Scores After Lumpectomy and Sentinel Lymph Node Biopsy with Multimodal Analgesia.

BACKGROUND: Multimodal analgesia (MMA) during breast surgery reduces postoperative pain and opioid requirements, but the relative contribution of local anesthetic dosing as a component of MMA is not well defined among patients undergoing lumpectomy and sentinel lymph node biopsy (SLNB). PATIENTS AND METHODS: We identified consecutive patients who underwent lumpectomy and SLNB with MMA from 1/2019 to 4/2020. Univariable and multivariable linear and logistic regression were used to examine associations between local anesthetics, opioid requirements in the post-anesthesia care unit (PACU), and pain scores in the PACU and on postoperative day (POD) 1. RESULTS: In total, 1603 patients [median tumor size, 14 mm (interquartile range 8-20 mm)] were included. The median PACU opioid requirement was 0 morphine milligram equivalents (interquartile range 0-5). PACU maximum pain was none or mild in 58% of patients and moderate to severe in 42%; among 420 survey respondents, 56% reported no or mild pain and 44% reported moderate to severe pain on POD 1. On multivariable analysis that adjusted for routine components of MMA, increasing doses of 0.5% bupivacaine were associated with reduced PACU opioid requirements (ß -0.04, 95% confidence interval -0.07 to -0.01, p = 0.011) and lower odds of moderate to severe pain (odds ratio 0.98, 95% confidence interval 0.97-0.99, p < 0.001). Local anesthetics were not associated with pain scores on POD 1. CONCLUSIONS: Higher amounts of local anesthetics reduce acute postoperative pain and opioid requirement after lumpectomy and SLNB. Maximizing dosing within weight-based limits is a low-risk, cost-effective pain control strategy that can be used in diverse practice settings.

Postdischarge Nonsteroidal Anti-Inflammatory Drugs Are not Associated with Risk of Hematoma after Lumpectomy and Sentinel Lymph Node Biopsy with Multimodal Analgesia.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly used in ambulatory breast surgery. The risk of hematoma associated with intraoperative ketorolac is low, but whether concomitant routine discharge with NSAIDs increases the risk of hematoma is unclear. METHODS: We retrospectively identified patients who underwent lumpectomy and sentinel lymph node biopsy (SLNB), and compared the 30-day risk of hematoma between patients discharged with opioids (opioid period: January 2018-August 2018) and patients discharged with NSAIDs with or without opioids (NSAID period: January 2019-April 2020). The association between study period and hematoma risk was assessed using multivariable models. Covariates included intraoperative ketorolac, home aspirin, and race/ethnicity. During the NSAID period, a survey was used to assess analgesic consumption on postoperative days 1-5. RESULTS: In total, 2724 patients were identified: 858 (31%) in the opioid period and 1866 (69%) in the NSAID period. In the NSAID period, 867 (46%) received NSAIDs and opioids, and 999 (54%) received NSAIDs only. Receipt of intraoperative ketorolac was higher in the NSAID period (78 vs. 64%, P < 0.001). The risks of any hematoma (4.1 vs. 3.6%, P = 0.6) and reoperation for bleeding (0.5 vs. 0.6%, P = 0.8) were similar between groups. Study period was not associated with hematoma risk (odds ratio 0.87, 95% confidence interval 0.56-1.35, P = 0.5). Among survey respondents (41%), nonopioid analgesic consumption did not increase after opioids were removed from the discharge regimen (median, 6 pills/group, P = 0.06). CONCLUSIONS: NSAIDs are associated with a low risk of hematoma after lumpectomy and SLNB, and should be prescribed instead of opioids, unless contraindicated.

Factors Associated with SARS-CoV-2 Infection in Physician Trainees in New York City during the First COVID-19 Wave.

Occupational and non-occupational risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported in healthcare workers (HCWs), but studies evaluating risk factors for infection among physician trainees are lacking. We aimed to identify sociodemographic, occupational, and community risk factors among physician trainees during the first wave of coronavirus disease 2019 (COVID-19) in New York City. In this retrospective study of 328 trainees at the Mount Sinai Health System in New York City, we administered a survey to assess risk factors for SARS-CoV-2 infection between 1 February and 30 June 2020. SARS-CoV-2 infection was determined by self-reported and laboratory-confirmed IgG antibody and reverse transcriptase-polymerase chain reaction test results. We used Bayesian generalized linear mixed effect regression to examine associations between hypothesized risk factors and infection odds. The cumulative incidence of infection was 20.1%. Assignment to medical-surgical units (OR, 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care, and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Caring for unfamiliar patient populations was protective (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not statistically significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for physician trainees responding to the COVID-19 pandemic.

Reconstruction in Women with T4 Breast Cancer after Neoadjuvant Chemotherapy: When Is It Safe?

BACKGROUND: Despite limited evidence regarding its safety, immediate reconstruction (IR) is increasingly offered to women with T4 breast cancer. We compared outcomes after IR, delayed reconstruction (DR), and no reconstruction (NR) in patients treated with neoadjuvant chemotherapy (NAC) and postmastectomy radiation therapy (PMRT) for T4 disease. STUDY DESIGN: We retrospectively identified consecutive women with T4 tumors treated with trimodality therapy from January 2007 through December 2019. Clinicopathologic characteristics, complications requiring reoperation, time to PMRT, and recurrence patterns were compared. The cumulative incidence of local recurrence (LR) was estimated using Kaplan-Meier methods. RESULTS: Of the 269 women identified, the median (IQR) age was 52 (45-62) years; 164 women (61%) had T4d disease. Forty-five women (17%) had IR, 41 (15%) had DR, and 183 (68%) had NR. IR was independently associated with T4a-c disease (odds ratio [OR], 5.75; 95% CI, 2.57-12.87; p < 0.001) and younger age (OR 0.91; 95% CI, 0.86-0.94; p < 0.001). The risk of complications after IR was 22% overall and 46% in T4d patients (6/13), compared with 4.4% overall for NR and 7.3% for DR (p < 0.001). IR was associated with >8-week interval to PMRT (p < 0.001). At a median (range) follow-up of 4.2 (0.2-13) years, the median time to first recurrence was 18 months and was similar between groups (p = 0.13). The cumulative incidence of LR was 16% for T4d disease and 2.2% for T4a-c disease (p < 0.001). CONCLUSIONS: After IR, women with T4 tumors, particularly T4d disease, experienced delayed initiation of adjuvant treatment and substantial morbidity, suggesting that an interval of >18 months between mastectomy and reconstruction is advisable.

Tumor-Nipple Distance of ≥ 1 cm Predicts Negative Nipple Pathology After Neoadjuvant Chemotherapy.

BACKGROUND: As neoadjuvant chemotherapy (NAC) for breast cancer has become more widely used, so has nipple-sparing mastectomy. A common criterion for eligibility is a 1 cm tumor-to-nipple distance (TND), but its suitability after NAC is unclear. In this study, we examined factors predictive of negative nipple pathologic status (NS-) in women undergoing total mastectomy after NAC. METHODS: Women with invasive breast cancer treated with NAC and total mastectomy from August 2014 to April 2018 at our institution were retrospectively identified. Following review of pre- and post-NAC magnetic resonance imaging (MRI) and mammograms, the association of clinicopathologic and imaging variables with NS- was examined and the accuracy of 1 cm TND on imaging for predicting NS- was determined. RESULTS: Among 175 women undergoing 179 mastectomies, 74% of tumors were cT1-T2 and 67% were cN+ on pre-NAC staging; 10% (18/179) had invasive or in situ carcinoma in the nipple on final pathology. On multivariable analysis, after adjusting for age, grade, and tumor stage, three factors, namely number of positive nodes, pre-NAC nipple-areolar complex retraction, and decreasing TND, were significant predictors of nipple involvement (p < 0.05). The likelihood of NS- was higher with increasing TND on pre- and post-NAC imaging (p < 0.05). TND ≥ 1 cm predicted NS- in 97% and 95% of breasts on pre- and post-NAC imaging, respectively. CONCLUSIONS: Increasing TND was associated with a higher likelihood of NS-. A TND ≥ 1 cm on pre- or post-NAC imaging is highly predictive of NS- and could be used to determine eligibility for nipple-sparing mastectomy after NAC.