The Presence of Extensive Lymphovascular Invasion is Associated With Higher Risks of Local-Regional Recurrence Compared With Usual Lymphovascular Invasion in Curatively Treated Breast Cancer Patients.

PURPOSE: Several data sets have demonstrated a correlation between lymphovascular invasion (LVI) and locoregional recurrence (LRR). Whether the observation of "extensive LVI" is a further and incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by (1) absence of LVI (neg), (2) LVI focal or suspicious (FS-LVI), (3) usual (nonextensive) LVI (LVI), and (4) extensive LVI (E-LVI). METHODS AND MATERIALS: Between December 2009 and August 2021, 8837 patients with early-stage breast cancer were treated with curative intent and were evaluable. Clinical-pathologic details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. A matched propensity score analysis compared outcomes between patients with LVI versus E-LVI. RESULTS: Of the 8837 patients studied, 5584 were negative, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. Patients with E-LVI had an adverse risk profile compared with the other groups. The 5- and 10-year LRR cumulative incidence estimates in patients with E-LVI were 9.6% (95% CI, 7.1-13) and 13% (95% CI, 10-17), respectively, which were significantly higher than those observed in the usual LVI group (6.8% [5.7-7.9] and 10% [8.8-12], respectively). A statistically significant difference in LRR was demonstrated in univariable (HR, 1.4; 95% CI, 1.03-1.89; P = .029) and multivariable regression analysis (HR, 1.62; 95% CI, 1.15-2.27; P = .005) compared with nonextensive LVI. In an alternative approach, we performed a 2:1 propensity score matching analysis comparing patients with LVI to those with E-LVI. The hazard ratio for LRR (HR, 1.47; CI 1.02-2.14; P = .041) was suggestive of a higher risk associated with E-LVI. CONCLUSIONS: Our work suggests that patients with E-LVI are at a higher risk for LRR than those with usual LVI. For patients who are borderline candidates for regional nodal irradiation or post-mastectomy radiation therapy, the finding of E-LVI might be decisive in favor of intensified treatment.

Reducing Disparities: Regional Anesthesia Blocks for Mastectomy with Reconstruction Within Standardized Regional Anesthesia Pathways.

BACKGROUND: Recent data suggest disparities in receipt of regional anesthesia prior to breast reconstruction. We aimed to understand factors associated with block receipt for mastectomy with immediate tissue expander (TE) reconstruction in a high-volume ambulatory surgery practice with standardized regional anesthesia pathways. PATIENTS AND METHODS: Patients who underwent mastectomy with immediate TE reconstruction from 2017 to 2022 were included. All patients were considered eligible for and were offered preoperative nerve blocks as part of routine anesthesia care. Interpreters were used for non-English speaking patients. Patients who declined a block were compared with those who opted for the procedure. RESULTS: Of 4213 patients who underwent mastectomy with immediate TE reconstruction, 91% accepted and 9% declined a nerve block. On univariate analyses, patients with the lowest rate of block refusal were white, non-Hispanic, English speakers, patients with commercial insurance, and patients undergoing bilateral reconstruction. The rate of block refusal went down from 12 in 2017 to 6% in 2022. Multivariable logistic regression demonstrated that older age (p = 0.011), Hispanic ethnicity (versus non-Hispanic; p = 0.049), Medicaid status (versus commercial insurance; p < 0.001), unilateral surgery (versus bilateral; p = 0.045), and reconstruction in earlier study years (versus 2022; 2017, p < 0.001; 2018, p < 0.001; 2019, p = 0.001; 2020, p = 0.006) were associated with block refusal. CONCLUSIONS: An established preoperative regional anesthesia program with blocks offered to all patients undergoing mastectomy with TE reconstruction can result in decreased racial disparities. However, continued differences in age, ethnicity, and insurance status justify future efforts to enhance preoperative educational efforts that address patient hesitancies in these subpopulations.

Patient and procedure characteristics associated with postoperative pain after prophylactic versus therapeutic ambulatory bilateral breast surgery.

BACKGROUND AND OBJECTIVES: We investigated whether age, body mass index (BMI), and tissue expander placement were related to postoperative opioid requirement for patients undergoing therapeutic versus prophylactic breast surgery. METHODS: Postoperative opioid consumption was evaluated for patients who underwent bilateral mastectomy with immediate implant-based reconstruction at a freestanding ambulatory cancer surgery center between 2016 and 2021. Ordinal regression tested whether surgical indication was associated with increased postoperative opioid requirements after adjusting for age, BMI, and tissue expander placement. RESULTS: Of 2447 patients, 6% underwent prophylactic surgeries. Therapeutic mastectomy patients had lower postoperative opioid requirement (OR = 0.67; 95% CI: 0.50-0.91; p = 0.030), but this was not significant after adjusting for covariates (OR = 0.75; 95% CI: 0.53-1.07; p = 0.2). Opioid use increased with higher BMI (OR = 1.06; 95% CI: 1.05-1.08; p < 0.001) and decreased with age (OR = 0.97; 95% CI: 0.96-0.98; p < 0.001) with therapeutic mastectomy patients being older (median 46 vs. 39). The subpectoral tissue expander group had nearly double the postoperative opioid requirement compared to prepectoral placement (OR = 1.86; 95% CI: 1.55-2.23; p < 0.001). CONCLUSIONS: Increased postoperative opioid requirement in women undergoing prophylactic procedures is best explained by age. Mastectomy patients should be counseled similarly about postoperative pain irrespective of indication. A larger prophylactic mastectomy sample is required to provide more precise estimates.

Strategies to avoid mastectomy skin-flap necrosis during nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy is associated with a higher risk of mastectomy skin-flap necrosis than conventional skin-sparing mastectomy. There are limited prospective data examining modifiable intraoperative factors that contribute to skin-flap necrosis after nipple-sparing mastectomy. METHODS: Data on consecutive patients undergoing nipple-sparing mastectomy between April 2018 and December 2020 were recorded prospectively. Relevant intraoperative variables were documented by both breast and plastic surgeons at the time of surgery. The presence and extent of nipple and/or skin-flap necrosis was documented at the first postoperative visit. Necrosis treatment and outcome was documented at 8-10 weeks after surgery. The association of clinical and intraoperative variables with nipple and skin-flap necrosis was analysed, and significant variables were included in a multivariable logistic regression analysis with backward selection. RESULTS: Some 299 patients underwent 515 nipple-sparing mastectomies (54.8 per cent (282 of 515) prophylactic, 45.2 per cent therapeutic). Overall, 23.3 per cent of breasts (120 of 515) developed nipple or skin-flap necrosis; 45.8 per cent of these (55 of 120) had nipple necrosis only. Among 120 breasts with necrosis, 22.5 per cent had superficial, 60.8 per cent had partial, and 16.7 per cent had full-thickness necrosis. On multivariable logistic regression analysis, significant modifiable intraoperative predictors of necrosis included sacrificing the second intercostal perforator (P = 0.006), greater tissue expander fill volume (P < 0.001), and non-lateral inframammary fold incision placement (P = 0.003). CONCLUSION: Modifiable intraoperative factors that may decrease the likelihood of necrosis after nipple-sparing mastectomy include incision placement in the lateral inframammary fold, preserving the second intercostal perforating vessel, and minimizing tissue expander fill volume.

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.

Paravertebral Blocks in Tissue Expander Breast Reconstruction: Propensity-Matched Analysis of Opioid Consumption and Patient Outcomes.

BACKGROUND: The paravertebral block (PVB) is an adjunctive perioperative pain control method for patients undergoing breast reconstruction that may improve perioperative pain control and reduce narcotic use. This study determined the efficacy of preoperative PVBs for perioperative pain management in patients undergoing tissue expander breast reconstruction. METHODS: A retrospective review was performed of patients who underwent tissue expander breast reconstruction from December of 2017 to September of 2019. Two patients with PVBs were matched using propensity scoring to one no-block patient. Perioperative analgesic use, pain severity scores on days 2 to 10 after discharge, and BREAST-Q Physical Well-Being scores before surgery and at 2 weeks, 6 weeks, and 3 months after surgery were compared between the two groups. RESULTS: The propensity-matched cohort consisted of 471 patients (314 PVB and 157 no block). The PVB group used significantly fewer morphine milligram equivalents than the no-block group (53.7 versus 69.8; P < 0.001). Average daily postoperative pain severity scores were comparable, with a maximum difference of 0.3 points on a 0-point to 4-point scale. BREAST-Q Physical Well-Being scores were significantly higher for the PVB group than the no-block group at 6 weeks after surgery (60.6 versus 51.0; P = 0.015) but did not differ significantly at 2 weeks or 3 months after surgery. CONCLUSIONS: PVBs may help reduce perioperative opioid requirements but did not reduce pain scores after discharge when used as part of an expander-based reconstruction perioperative pain management protocol. Continued research should examine additional or alternative regional block procedures as well as financial cost and potential long-term impact of PVBs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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.

Nipple-Sparing Mastectomy and Immediate Reconstruction: A Propensity Score-Matched Analysis of Satisfaction and Quality of Life.

BACKGROUND: Although it is intuitive that nipple-sparing mastectomy in selected patients would result in excellent cosmetic outcomes and high patient satisfaction, studies of clinical outcomes and health-related quality of life are limited and show mixed results. This study aimed to use a propensity score-matching analysis to compare satisfaction and health-related quality-of-life outcomes in patients who underwent implant-based reconstruction following bilateral nipple-sparing mastectomy or skin-sparing mastectomy. METHODS: A propensity score-matching analysis (1:1 matching, no replacement) was performed comparing patients undergoing nipple-sparing or skin-sparing mastectomy with immediate bilateral implant-based breast reconstruction. Patients with a history of any radiation therapy were excluded. Matched covariates included age, body mass index, race, smoking history, neoadjuvant chemotherapy, bra size, and history of psychiatric diagnosis. Outcomes of interest included BREAST-Q scores and complications. RESULTS: The authors examined 1371 patients for matching and included 460 patients (nipple-sparing mastectomy, n = 230; skin-sparing mastectomy, n = 230) in the final analyses. The authors found no significant differences in baseline, cancer, and surgical characteristics between matched nipple-sparing and skin-sparing mastectomy patients, who also had similar profiles for surgical complications. Interestingly, the authors found that postoperative Satisfaction with Breasts scores and all other health-related quality-of-life domains were stable over a 3-year period and did not differ significantly between the two groups. CONCLUSIONS: Compared with skin-sparing mastectomy, bilateral nipple-sparing mastectomy did not improve patient-reported or clinical outcomes when combined with immediate implant-based reconstruction. The impact that nipple-sparing mastectomy may have on breast aesthetics and the ability of the BREAST-Q to gauge an aesthetic result following nipple-sparing mastectomy warrant further investigation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Who Are We Missing: Does Engagement in Patient-Reported Outcome Measures for Breast Cancer Vary by Age, Race, or Disease Stage?

INTRODUCTION: Patient-reported outcome measures (PROM) are used to assess value-based care. Little is known as to whether PROM response in breast cancer reflects the diverse patient population. The BREAST-Q, a validated measure of satisfaction and quality of life, and Recovery Tracker, a postoperative assessment tool, are PROM routinely delivered to all patients undergoing breast surgery at our institution. Here we determine whether response to PROM differs by age, race, language, or disease stage. METHODS: All patients who had a breast operation between January 2020 and July 2021 were requested to complete the BREAST-Q and Recovery Tracker. Non-responders did not complete the PROM at any timepoint; responders completed 1 or more. Primary outcomes included rates of non-response versus response overall. RESULTS: Of 6374 patients identified, 5653 (88.7%) responded to either PROM [4366/4751 (91.9%) BREAST-Q; 2746/3384 (81.1%) Recovery Tracker]. On univariate analysis, non-responders were older (60 years versus 55 years, p < 0.001) and more often non-English speaking (p < 0.001), Hispanic ethnicity (p = 0.031), and Black race (p < 0.001), versus responders. On multivariate analysis, non-responders were significantly more often Black race and non-English speaking (p < 0.001). Non-English speakers were significantly less responsive among all ethnicities and races except Black race. Although breast cancer stage did not reach significance for response, patients with malignant disease and those receiving neoadjuvant chemotherapy responded more often. CONCLUSIONS: Our findings demonstrate high patient engagement using 2 different PROM following breast surgery, but suggest that PROM results may not reflect the experience of the entire breast cancer population. Care process changes based solely on PROM should consider these findings to ensure that the views of the entire spectrum of patients with breast cancer are represented.

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial. METHODS: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). RESULTS: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. CONCLUSIONS: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this population.

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 Use of Pectoralis Blocks in Breast Surgery: A Practice Advisory and Narrative Review from the Society for Ambulatory Anesthesia (SAMBA).

Although pectoralis (PECS) blocks are commonly used for breast surgery, recommendations regarding the efficacy of these blocks have thus far not been developed by any professional anesthesia society. Given the potential impact of PECS blocks on analgesia after outpatient breast surgery, The Society for Ambulatory Anesthesia (SAMBA) convened a task force to develop a practice advisory on the use of this analgesic technique. In this practice advisory, we compare the efficacy of PECS blocks with systemic analgesia, local infiltration anesthesia, and paravertebral blockade. Our objectives were to advise on two clinical questions. (1) Does PECS-1 and/or -2 blockade provide more effective analgesia for breast-conserving surgery than either systemic analgesics or surgeon-provided local infiltration anesthesia? (2) Does PECS-1 and/or -2 blockade provide equivalent analgesia for mastectomy compared with a paravertebral block (PVB)? Among patients undergoing breast-conserving surgery, PECS blocks moderately reduce postoperative opioid use, prolong time to analgesic rescue, and decrease postoperative pain scores when compared with systemic analgesics. SAMBA recommends the use of a PECS-1 or -2 blockade in the absence of systemic analgesia (Strength of Recommendation A). No evidence currently exists that strongly favors the use of PECS blocks over surgeon-performed local infiltration in this surgical population. SAMBA cannot recommend PECS blocks over surgical infiltration (Strength of Recommendation C). For patients undergoing a mastectomy, a PECS block may provide an opioid-sparing effect similar to that achieved with PVB; SAMBA recommends the use of a PECS block if a patient is unable to receive a PVB (Strength of Recommendation A).

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.