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Sentinel Lymph Node Biopsy for Patients With cN1 HR+/HER2- Breast Cancer and Palpable Adenopathy: A Nonrandomized Clinical Trial

Mamtani, Anita; Pilewskie, Melissa; Wilson, Niamey; Chung Whang, Heiwon; Barrio, Andrea V; Bassin, Leah; Capko, Deborah; Choi, Daniel X; Cody, Hiram S; Downs-Canner, Stephanie; El-Tamer, Mahmoud; Gemignani, Mary L; Heerdt, Alexandra S; Kirstein, Laurie; Lee, Minna K; Mango, Victoria L; Montagna, Giacomo; Moo, Tracy-Ann; Oxenberg, Jacqueline; Plitas, George; Sabel, Michael; Sacchini, Virgilio; Sclafani, Lisa; Sevilimedu, Varadan; Tadros, Audree B; Van Zee, Kimberly J; Morrow, Monica
IMPORTANCE/UNASSIGNED:Randomized trials established the safety of omitting axillary lymph node dissection (ALND) among patients with clinically node-negative breast cancer and less than 3 positive sentinel lymph nodes (+SLNs) having upfront surgery and adjuvant radiation. Patients with palpable mobile level I/II axillary adenopathy (cN1) were not eligible for these studies. Presently, more than 80% of patients with HR+/HER2- cN1 disease undergo ALND either at upfront surgery or after neoadjuvant therapy, despite evidence that 50% to 60% will have only 1 or 2 positive nodes. OBJECTIVE/UNASSIGNED:To determine upfront sentinel lymph node biopsy (SLNB) feasibility and evaluate ALND rate among patients with HR+/HER2- cN1 breast cancer selected with axillary ultrasound (AUS). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This nonrandomized clinical trial involved patients with cTx/cT1-2 cN1 HR+/HER2- breast cancer with 3 or fewer morphologically abnormal nodes on AUS at 4 centers. The trial began on April 20, 2021, and the database for this report was frozen on September 26, 2024. INTERVENTIONS/UNASSIGNED:Patients underwent upfront lumpectomy/mastectomy and SLNB, with single/dual-tracer mapping. ALND was indicated for 3 or more positive SLNs. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was ALND rate. Secondary outcomes were frequency of palpable nodes being radioactive/blue and locoregional recurrence. RESULTS/UNASSIGNED:Among 78 enrolled patients, the median (IQR) age was 58 (49.0-66.5) years. Most tumors were cT1 (37 [47%]) or cT2 (40 [51%]), 56 patients (72%) had ductal histology, and 59 tumors (76%) were moderately differentiated. On AUS, 39 patients (50%) had 1 abnormal-appearing node, 33 (42%) had 2, and 6 (8%) had 3. Median (IQR) pathologic tumor size was 2.3 (1.6-3.3) cm, 50 patients (64%) had lymphovascular invasion, and 54 (69%) had extracapsular extension. SLNB was performed with dual tracer in 68 (87%), and 3 or more SLNs were retrieved in 75 (96%). The palpable diseased nodes were blue and/or radioactive in 107 of 161 instances (66.5%). Overall, 24 patients (31%) had 1 +SLN, 30 patients (38%) had 2 +SLNs, and 24 patients (31%) had 3 or more +SLNs. SLNB alone was performed in 59 patients (76%), while 19 (24%) had ALND; indicated ALND was deferred in 5 cases. Among those with 12 months or more follow-up (n = 68; median, 25 months), there have been no isolated axillary or locoregional recurrences. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study found that SLNB is feasible among patients with cN1 HR+/HER2- disease and that resection of palpable nodes is necessary to minimize false-negative rates. This approach affords the opportunity to omit ALND and minimize morbidity among patients with cN1 cancer and limited nodal burden. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04854005.
PMID: 42090164
ISSN: 2168-6262
CID: 6031292

Impact of Age on Outcomes in Women with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy

Matar-Ujvary, Regina; Fecanji, Kristina; Sevilimedu, Varadan; Montagna, Giacomo; Gemignani, Mary L
PURPOSE/OBJECTIVE:Previous literature suggests that age does not impact outcomes in women with triple-negative breast cancer (TNBC). Young women have a higher rate of achieving pathologic complete response (pCR); however, the impact of age on outcomes and the type of surgery performed following neoadjuvant chemotherapy (NAC) is not well studied. METHODS:An institutional retrospective database review identified women with TNBC who underwent NAC followed by surgery from 03/2010 to 09/2019. Clinicopathologic, treatment, and outcome variables were compared between women aged <40 and ≥40 years at diagnosis. The association between type of surgery and outcomes was examined. RESULTS:= 0.6). On multivariable analysis, lymphovascular invasion and nodal positivity were significantly associated with a decrease in overall and breast-cancer-specific survival. Age <40 years was not associated with survival. Women who opted for bilateral mastectomy were more likely to achieve a pCR. CONCLUSIONS:Young age was not an independent predictor of recurrence and survival outcomes in women with TNBC treated with NAC. Further studies with ongoing advancement in NAC are crucial.
PMID: 41700461
ISSN: 2156-535x
CID: 6004482

Perspectives of Young Women with Breast Cancer: Patient Experiences Indicate Opportunities to Improve Treatment

Myers, Sara P; Gilliland, Jaime; Goldfarb, Shari B; Gemignani, Mary L
In this focus group study of 11 women younger than 45 years of age treated at Memorial Sloan Kettering Cancer Center (New York, NY, USA) between March 2020 and April 2021, patients were asked about their preferences for types of resources, and timing and method of information delivery. Patients expressed interest in personalized medicine, access to integrative health and a holistic approach to treatment, and early consultation for fertility preservation. Their narratives elaborated on how age at diagnosis influences interpersonal relationships and quality of life, and provides direction for interventions to better counsel and support this population.
PMID: 39527023
ISSN: 2156-535x
CID: 5752642

Financial Toxicity Among Women with Breast Cancer Varies by Age and Race

Myers, Sara P; Aviki, Emeline; Sevilimedu, Varadan; Thom, Bridgette; Gemignani, Mary L
INTRODUCTION/BACKGROUND:Financial toxicity negatively affects clinical outcomes in breast cancer. Underrepresented demographics may be at higher risk for financial toxicity. We characterized disparities on the basis of age and other factors. PATIENTS AND METHODS/METHODS:Surveys completed by women with stage 0-IV breast cancer treated at Memorial Sloan Kettering Cancer Center between 06/2022 and 05/2023 were analyzed. The comprehensive score for financial toxicity (COST) scale was used to assess financial toxicity. Descriptive statistics were calculated for differences in financial toxicity/related factors, and outcomes by age and race. Associations between variables of interest and COST scores were analyzed using linear regression. RESULTS:Of 8512 respondents (75% white, 9.3% Asian, 8.4% Black), most (68%) had clinical stage 0/I disease. Stratified by age, young Black women had higher financial toxicity than young white or Asian women (p < 0.001). On multivariable analysis, women age < 45 years experienced higher financial toxicity than older women (coefficient - 2.0, 95% CI - 2.8 to - 1.1, p < 0.001). Compared with white women, financial toxicity was greater among Black (coefficient - 6.8, 95% CI - 7.8 to - 5.8) and Asian women (coefficient - 3.5, 95% CI - 4.4 to - 2.5). Cost-related medication non-adherence was more frequent among Black and Asian women (p < 0.001). Asian women more often paid for treatment with savings than white and Black women (p < 0.001). Young women reported using savings for treatment-related costs more than older (45% vs. 32%); p < 0.001). CONCLUSIONS:Racial minorities and young patients are disproportionately affected by financial toxicity. Further studies are planned to determine how financial toxicity evolves over time and whether referral to financial services effectively reduces toxicity.
PMID: 39078600
ISSN: 1534-4681
CID: 5678412

ASO Author Reflections: Young Adults and Racial Minorities May Be at High Risk for Financial Toxicity After Breast Cancer Treatment

Myers, Sara P; Aviki, Emeline; Sevilimedu, Varadan; Thom, Bridgette; Gemignani, Mary L
PMID: 39172300
ISSN: 1534-4681
CID: 5680902

Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis

Jones, V Morgan; Nelson, Jonas A; Sevilimedu, Varadan; Le, Tiana; Allen, Robert J; Mehrara, Babak J; Barrio, Andrea V; Capko, Deborah M; Heerdt, Alexandra S; Tadros, Audree B; Gemignani, Mary L; Morrow, Monica; Sacchini, Virgilio; Moo, Tracy-Ann
BACKGROUND:Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS/METHODS:Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS:A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS:Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.
PMID: 38990221
ISSN: 1534-4681
CID: 5678402

Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease

Zhang, Jennifer Q; Dos Anjos, Carlos Henrique; Sevilimedu, Varadan; Crown, Angelena; Amoroso, Kimberly A; Pilewskie, Melissa L; Robson, Mark E; Gemignani, Mary L
BACKGROUND:The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known. METHODS:Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer. RESULTS:The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138). CONCLUSIONS:Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.
PMCID:11005956
PMID: 37661222
ISSN: 1534-4681
CID: 5678392

Long-Term Patient-Reported Outcomes Comparing Oncoplastic Breast Surgery and Conventional Breast-Conserving Surgery: A Propensity Score-Matched Analysis

Pak, Linda M; Matar-Ujvary, Regina; Verdial, Francys C; Haglich, Kathryn A; Sevilimedu, Varadan; Nelson, Jonas A; Gemignani, Mary L
INTRODUCTION/BACKGROUND:Oncoplastic breast surgery (OBS) combines plastic surgery techniques with conventional breast-conserving surgery (BCS) and expands BCS eligibility. Limited data are available on patient-reported outcomes (PROs) after OBS. Here we compare long-term PROs after OBS and BCS utilizing the BREAST-Q. PATIENTS AND METHODS/METHODS:Women undergoing OBS or BCS between 2006 and 2019 who completed ≥ 1 long-term BREAST-Q survey 3-5 years postoperatively were identified. Baseline characteristics were compared between women who underwent OBS/BCS. Women who underwent OBS were paired with those who underwent BCS using 1:2 propensity matching [by age, body mass index (BMI), race, T stage, and multifocality]. BREAST-Q scores were compared preoperatively and 3-5 years postoperatively. RESULTS:A total of 297 patients were included for analysis (99 OBS/198 BCS). Women who underwent OBS were younger (p < 0.001) and had higher BMI (p = 0.005) and multifocal disease incidence (p = 0.004). There was no difference between groups in nodal stage, re-excision rates, axillary surgery, chemotherapy, endocrine therapy, or radiotherapy. After propensity matching preoperatively, women who underwent OBS reported lower psychosocial well-being (63 versus 100, p = 0.039) but similar breast satisfaction and sexual well-being compared with women who underwent BCS; however, only three patients who underwent BCS had preoperative BREAST-Q scores available for review. In long-term follow-up, women who underwent OBS reported lower psychosocial scores (74 versus 93, p = 0.011) 4 years postoperatively, but not at 5 years (76 versus 77, p = 0.83). There was no difference in long-term breast satisfaction or sexual well-being. CONCLUSIONS:Women who undergo OBS present with a larger disease burden and may represent a group of non-traditional BCS candidates; they reported similar long-term breast satisfaction and sexual well-being compared with women who undergo BCS. While women who underwent OBS reported lower psychosocial well-being scores preoperatively and during a portion of the follow-up period, this difference was no longer seen at 5 years postoperatively.
PMCID:10996134
PMID: 37556008
ISSN: 1534-4681
CID: 5678382

The Impact of Breast-Conserving Surgery Re-excision on Patient-Reported Outcomes Using the BREAST-Q

Matar-Ujvary, Regina; Haglich, Kathryn; Flanagan, Meghan R; Fuzesi, Sarah; Sevilimedu, Varadan; Nelson, Jonas A; Gemignani, Mary L
BACKGROUND:Approximately 14% of women undergoing breast-conserving surgery (BCS) require re-excision to achieve negative margins following the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) margin guidelines, which may influence patient-reported outcomes (PROs). Few studies have assessed the impact of re-excision on PROs following BCS. PATIENTS AND METHODS/METHODS:Women with stage 0-III breast cancer undergoing BCS who completed a BREAST-Q PRO measure from 2010 to 2016 were identified from a prospective database. Baseline characteristics were compared between women who underwent one BCS and those who underwent ≥ 1 re-excision surgery for positive margins (R-BCS). Linear mixed models were used to analyze associations between number of excisions and BREAST-Q scores over time. RESULTS:Of 2543 eligible women, 1979 (78%) had one BCS and 564 (22%) had R-BCS. Younger age, lower BMI, surgery pre-SSO Invasive Guidelines issuance, ductal carcinoma in situ (DCIS), multifocal disease, radiation therapy receipt, and endocrine therapy omission were more common in the R-BCS group. Breast satisfaction and sexual well-being were lower in the R-BCS group 2 years postoperatively. There were no differences in psychosocial well-being between groups over 5 years. On multivariable analysis, re-excision was associated with lower breast satisfaction and sexual well-being (p= 0.007 and p= 0.049, respectively), but there was no difference in psychosocial well-being (p= 0.250). CONCLUSIONS:Women with R-BCS had lower breast satisfaction and sexual well-being 2 years postoperatively, but this difference did not remain long term. Psychosocial well-being in women who underwent one BCS were largely comparable over time to the R-BCS group. These findings may help in counseling women who are concerned about satisfaction and quality-of-life outcomes with BCS if re-excision is necessary.
PMCID:10782578
PMID: 37306849
ISSN: 1534-4681
CID: 5678362

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

Moo, Tracy-Ann; Nelson, Jonas A; Sevilimedu, Varadan; Charyn, Jillian; Le, Tiana V; Allen, Robert J; Mehrara, Babak J; Barrio, Andrea V; Capko, Deborah M; Pilewskie, Melissa; Heerdt, Alexandra S; Tadros, Audree B; Gemignani, Mary L; Morrow, Monica; Sacchini, Virgilio
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.
PMCID:10517092
PMID: 37178195
ISSN: 1365-2168
CID: 5678372