Mrdutt, Mary M.

PURPOSE Over 50% of households in the United States have at least one musician—many musicians are also breast cancer survivors. This group has not been well studied, and given the level of fine sensory-motor skill required for musicianship, we hypothesized that musicians experience unique manifestations of breast cancer treatment toxicities. METHODS A nine-item Musical Toxicity Questionnaire (MTQ) was distributed to patients who had consented to participate in the Mayo Clinic Breast Cancer Registry. The MTQ screened participants by asking if they played a musical instrument or sang in the last 10 years: questions populated for those who answered yes. Respondents were asked if they noticed difficulty with their musical endeavor during or after breast cancer treatment, defined as acute musical toxicity (AMT). The questionnaire asked which side effect and cancer-directed therapy most influenced musical ability, what musical attributes were affected, and the timeline of resolution. Multivariable and classification tree analyses assessed relationships between AMT and treatment characteristics. RESULTS Of 1,871 survey respondents, 29% (535/1,871) self-identified as musicians. Over a quarter (27%, 144/535) reported AMT, and for 57% (82/144), AMT had not resolved at the time of survey. Of the treatments each participant received, chemotherapy was most often reported as most negatively impactful (63/89 who received chemotherapy, 71%). Decreased endurance was the most common musical difficulty (64% of those with AMT, 92/144), followed by decreased accuracy, trouble playing/singing quickly, and difficulty using proper technique. Multivariable and classification tree analyses revealed that receipt of chemotherapy was most strongly correlated with AMT. CONCLUSION These results will help oncology care teams counsel musicians, answer questions about impacts on musicality, and provide a timeline for resolution of musical symptoms.

PURPOSE The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

12048 Background: Playing music has been an important part of human culture for millennia. Today more than half of American households have at least one person who plays music, and in the UK 43% of adults play an instrument. Despite the overlap between musicians and people diagnosed with cancer, the effect of cancer treatment on musicianship has not been well-studied. We previously reported that 26% of a musician breast cancer survivor cohort reported difficulty with musicianship after treatment, and here we conduct further analysis to identify treatment and disease factors associated with this difficulty, termed acute musical toxicity (AMT). Methods: The Musical Toxicity Questionnaire was distributed to participants who had previously enrolled in the Mayo Clinic Breast Cancer Registry. PROMIS (Patient-Reported Outcomes Measurement Information System) scores were available through the Registry and treatment details were collected retrospectively. Due to the inter-dependency and high correlation between treatment and disease-related variables, a classification tree analysis (CTA) was performed to identify the combination of variables that most accurately classified patients by AMT. Sixteen variables were analyzed by the algorithm. Logistic regression was utilized for examining associations between AMT and continuous variables. Results: Of the 4075 surveys distributed, 1871 were returned and 535 respondents identified as musicians. Median time from diagnosis was 5.2 years, respondents were mostly stage I or II (71%), and 32% were node positive (N+). Over a quarter (26% or 144 respondents) reported AMT. In the final CTA model, being N+ was strongly associated with AMT (42% of those N+ had AMT, 20% of those not N+ had AMT). For respondents who were N+, those who received endocrine therapy were more likely to have AMT than those who did not (46% vs 21% respectively). Subsequent leaves identified not undergoing axillary lymph node dissection (ALND) and receiving chemotherapy as associated with AMT. For respondents who did not receive chemotherapy, breast reconstruction was associated with AMT (60% vs 19%). Variables such as mastectomy, radiation volume, specific chemotherapies, and stage of disease were not selected by the algorithm. The odds of having AMT decreased by 9.7% and 17% with each additional point in the composite mental health (p=0.003) and physical health (p<0.001) PROMIS scores, respectively. The odds of having AMT increased by 3.5% with each lymph node removed (p=0.001). Conclusions: The final model suggests that the group with the largest proportion of AMT was N+, received endocrine therapy, did not have ALND, and received chemotherapy. Both physical and mental health PROMIS scores were associated with AMT, although the directionality of this relationship requires more study. Care teams should counsel patients on potential musical toxicity and engage in shared decision making with musical patients.

Abstract Background: In patients with micro- and macrometastases in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC), additional positive nodes are found in &gt;60% of cases and axillary lymph node dissection (ALND) is currently considered standard of care. The likelihood of finding additional positive lymph nodes in patients with residual isolated tumor cells (ITCs) is unknown, and the benefit of ALND is unclear. As a consequence, surgical management of the axilla in these patients is not standardized. We sought to evaluate how often additional positive lymph nodes are found, to determine factors associated with ALND, and to compare oncological outcomes in patients treated with and without ALND after identification of residual ITCs in the SLN. Methods: Data were collected from 42 centers: 20 in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks, and 22 in North and South America. We included patients with cT1-4 N0-3 breast cancer at diagnosis who underwent NAC followed by axillary staging with either SLN biopsy (SLNB) or targeted axillary dissection (TAD) and were found to have residual ITCs [ypN0(i+)]. Single-tracer mapping was allowed for cN0 patients, while dual mapping or TAD was required for cN+ cases. Axillary treatment included completion ALND and/or nodal radiotherapy (RT). Competing risk analysis was performed to assess the cumulative incidence rates of any axillary recurrence (AR), locoregional recurrence (LRR), and any invasive (locoregional or distant) recurrence. Five-year cumulative incidence rates were compared between patients who underwent ALND and those who did not using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 412 patients treated with NAC followed by surgery from 01/2009-05/2022. 146 (35.4%) had completion ALND and 266 (64.6%%) did not. Median patient age was 48 years. The majority (57%) of patients had clinical T2 tumors, and 68% had biopsy-proven N1 disease. Most were HR+/HER2- (41%) or HER2+ (39%). Most patients (80%) received anthracycline and taxane-based chemotherapy regimens. Nodal RT was administered to 83% of patients. The median number of SLNs with ITCs was 1. Patients treated with ALND were more likely to have ITCs detected on frozen section (61% v 6.7%, p&lt; 0.001), to have N2/3 disease at presentation (15.1% v 5.6%, p=0.001) and to have LVI (40% v 26%, p=0.004) (Table 1). There was no significant trend over time in the proportion of patients undergoing completion ALND during the study period (p=0.5). In the ALND group, additional positive nodes were found in 43/146 (29.5%) of cases, and consisted of macrometastases in 11/146 (7.5%), micrometastases in 9/146 (6.2%), and ITCs in 23/146 (15.8%). 5-year rates of any AR, LRR, and any invasive recurrence in the entire cohort were 2.7% (95% CI 1.2-5.4), 2.8% (95% CI 1.2-5.4) and 16% (95% CI 11-21), respectively. There was no statistical difference between patients who underwent ALND and those who did not in any of the 3 endpoints (2.2% v 3.1%, p=0.6), (2.6% v 3.0%, p=0.4) and (14% v 18%, p=0.12), respectively. Conclusion: The likelihood of finding additional positive lymph nodes in patients with ITCs after NAC is lower than in patients with residual micro- and macrometastases, and in the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population. Overall, these results do not support routine ALND in patients with residual ITCs. Table 1. Clinicopathological Features of the Study Cohort, Stratified by Type of Axillary Surgery Frequency (row percent) reported for categorical variables, and median (IQR) reported for continuous variables. SLNB sentinel lymph node biopsy; TAD targeted axillary dissection; SLNs sentinel lymph nodes; LNs lymph nodes; pCR pathologic complete response; ACT anthracycline and taxane; AC anthracycline; H Herceptin, HP, Herceptin and Perjeta; TC taxol (or Taxotere) and carboplatinum; LVI lymphovascular invasion; BCS breast-conserving surgery. ^ Applied to HER2- tumors only (n=252). ^^ Applies to HER2+ tumors only (n=160). # LVI was present on core biopsy or final pathology. * Applies to BCS patients only (n=175). ** Applies to mastectomy patients only (n=237). Citation Format: Giacomo Montagna, Alison Laws, Massimo Ferrucci, Mary Mrdutt, Natália Polidorio, Varadan Sevilimedu, Tracy-Ann Moo, Andrea Barrio, Marissa K. Boyle, Flavia Vidal Cabero, Daniela Cocco, Fabio Corsi, Angelena Crown, Meghan R. Flanagan, Mehmet Ali Gulcelik, Callie Hlavin, Justyna Jelinska, Hasan Karanlik, Susan Kesmodel, Henry Kuerer, Sherko Küemmel, Cornelia Leo, Tehillah Menes, Melissa Pilewskie, Nina Pislar, Nicola Rocco, Jai Min Ryu, Leonardo Soares, Christoph Tausch, M. Umit Ugurlu, CICERO URBAN, Astrid Botty van de Bruele, Denise Vorburger, Fredrik Wärnberg, Anna Weiss, Austin Williams, Stephanie Wong, Steven G. Woodward, Susie X. Sun, Jennifer Q. Zhang, M. Firdos Ziauddin, Guldeniz Karadeniz Cakmak, Nuran Bese, Thorsten Kühn, Judy Boughey, Tari King, Nina Ditsch, Maggie Banys-Paluchowski, Monica Morrow, Walter Weber. Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-02.

Abstract Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p&lt; 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p&lt; 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p&lt; 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-02.