Summary:. This article reviews current practices and challenges in breast cancer screening for transgender individuals undergoing gender-affirming chest surgery, highlighting the unique role of plastic surgeons in long-term oncological care. As masculinizing mastectomies become more common, concerns persist regarding residual breast tissue and cancer risk. Although surgery substantially reduces risk—comparable to the protective effect of reduction mammaplasty in cisgender women—it does not eliminate risk entirely, as 1%–2% of breast tissue typically remains. Patient-driven aesthetic decisions may further influence oncological risk and complicate imaging, underscoring the importance of patient education and ongoing surveillance. The effects of exogenous hormones on breast cancer risk remain incompletely defined. Feminizing hormone therapy, family history, and obesity are established risk factors in cisgender women, but their independent contribution to risk in transgender women remains under investigation. Patients with genetic predisposition or strong family history should be referred to breast oncology specialists for individualized risk assessment. Systemic barriers—including delayed initiation of imaging, limited primary care–based risk assessment, and inconsistent insurance coverage—position plastic surgeons to address critical gaps in care. Recommended practices include annual clinical chest examinations for transgender men following mastectomy, continuation of age-appropriate screening for transgender women on long-term estrogen therapy, and routine documentation of counseling and referrals to ensure continuity of care. By integrating epidemiological data, practice surveys, and surgical considerations, this article provides a distinct specialty perspective and calls for interdisciplinary collaboration to establish evidence-based screening protocols for this growing patient population.

Introduction Prior studies have demonstrated variation in surgical management of breast cancer. As randomized controlled trials have increasingly shown a limited survival advantage with surgery in stage IV breast cancer, the present study aimed to assess geographic and institutional variations in locoregional surgical management of de novo stage IV breast cancer. Methods We conducted a retrospective cohort analysis of 68,670 patients with de novo stage IV breast cancer from 2012 to 2021 using the National Cancer Database. The proportion of patients treated with surgical resection was compared between year of diagnosis, facility type, geographic region, and facility volume while controlling for demographic and clinical variables. Results Overall, 17,620 patients (25.7%) with de novo stage IV breast cancer underwent breast, axillary, or metastatic site surgical resection. There was a statistically significant decrease from 27.4 to 15.0% in the proportion of patients undergoing primary tumor resection over the included timeframe (p < 0.001). Significant variation was noted in the proportion of patients receiving primary tumor resection among geographic regions, ranging from 14.9 to 23.2% (Northeast and West, p < 0.001). Patients treated at comprehensive community cancer centers were most likely to have primary site surgery, and those treated at academic centers (including National Cancer Institute-designated comprehensive cancer centers) were least likely (22.1 vs. 16.7%, respectively, p < 0.001). Conclusion Significant variation exists in locoregional surgical management of de novo stage IV breast cancer. Surgical intervention has decreased over time, but this study reveals that institutional and geographic factors are associated with the surgical management for these patients.

Importance:Single-fraction preoperative ablative stereotactic partial breast irradiation (sPBI) can be safely delivered in early-stage hormone receptor-positive (HR+) breast cancer with delayed time to surgery and high pathologic complete response rates. Objectives:To examine the maximum tolerated dose (MTD) of sPBI and to evaluate clinical outcomes, including pathological complete response (pCR), time to surgery, and toxic effects, associated with dose escalation. Design, Setting, and Participants:This phase 1 nonrandomized clinical trial of dose escalation enrolled patients with HR+, ERBB2-negative, cN0 invasive breast cancer not requiring chemotherapy from a single academic center between December 2019 and April 2024. Interventions:Patients were treated with 30, 34, or 38 Gy using MR-guided linear accelerator (MR-LINAC), robotic radiosurgery, or cobalt stereotactic unit. Patients received endocrine therapy and delayed surgery (≤12 months). Main Outcomes and Measures:The MTD was evaluated using dose-limiting toxicity (DLT), defined as grade 3 or higher toxic effects within 90 days. Additionally, pCR, near pCR (npCR), the association of dose escalation with time to surgery, local control, surgical morbidity, and cosmesis were evaluated. Results:A total of 44 patients (median [range] age, 64.5 [44.0-77.0] years) were treated, with 14 (31.8%) receiving 30 Gy (median [IQR] follow-up, 52.0 [28.2-54.5] months), 15 (34.1%) receiving 34 Gy (median [IQR] follow-up, 40.0 [36.5-41.0] months), and 15 (31.4%) receiving 38 Gy (median [IQR] follow-up, 20.0 [17.0-22.0] months). MTD was not reached. pCR rates were 35.7% (5 patients), 46.7% (7 patients), and 66.7% (10 patients), while pCR with npCR rates were 64.3% (9 patients), 93.3% (14 patients), and 93.3% (14 patients), respectively. Local control was 100%, and surgical morbidity was 2.2% (1 of 44 patients). The mean (SD) Ki-67 was 11.3% (6.4%) at diagnosis, and on evaluable residual disease, it was 1.9% (2.0%) (P < .001). A time-to-surgery threshold of 277 days was the optimal cutoff for pCR (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.62-0.91). In patients with surgery more than 9 months after sPBI, pCR rates were 100% (5 of 5 patients), 66.7% (4 of 6 patients), and 64.3% (9 of 14 patients) (P = .40), and combined pCR and npCR rates were 100%, 83.3% (5 patients), and 92.9% (13 patients) (P = .69) for the 30, 34, and 38 Gy groups, respectively. For all patients who received surgery more than 9 months after sPBI, the pCR rate was 72.0% (18 of 25 patients). Longer time to surgery was associated with pCR (odds ratio, 1.02; 95% CI, 1.01-1.03; P = .005), while higher radiation dose was not. Acute toxic effects included 32 grade 1, 3 grade 2 (breast pain and dermatitis), and 1 late grade 3 (wound dehiscence in patient with uncontrolled diabetes) events. Cosmesis remained stable at 36 months. Conclusions and Relevance:In this nonrandomized clinical trial, the rate of toxic effects was low, and treatments were tolerable up to 38 Gy. Delaying surgery more than 9 months after sPBI with endocrine therapy was associated with increased pCR and npCR (>90%), while higher doses were not. These findings support further investigation of sPBI as a potential nonsurgical approach for selected patients with early-stage HR+ breast cancers. Trial Registration:ClinicalTrials.gov Identifier: NCT04040569.

Purpose/Objective(s) We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using a cobalt stereotactic radiation system. Materials/Methods Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity graded (using the NCI version 5.0 and RTOG/EORTC late radiation scale). Results From March 2019 to October /2021, 74 patients were treated respectively. Of these, 38 were treated to 40 Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 36 months (mo), range (r) 3-58 mo. Median age was 63 years (r = 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. Fort-five of 46 invasive tumors were ER+. Sixty of 74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 225 acute grade 1 toxicities, and 30 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (12), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 103 Grade 1 late toxicities, 3 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis 1, and pain (2). Three patients developed grade 1 asymptomatic nonpalpable fat necrosis. The most common grade 1 late toxicities were breast pain (25), hyperpigmentation (11), fibrosis (11), and fatigue (5). Physicians scored cosmesis excellent or good 71/74 (95.9%), 59/61 (96.7%), 61/62 (98.3%), 33/33(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 63/72 (87.5%), 54/60 (90.0%), 57/64 (89.0%), 35/37 (94.6%). There have been no local regional or distant disease recurrences. Conclusion Results at 36-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Clinical trials.gov identifier is NCT03581136.

Importance Single-fraction preoperative ablative stereotactic partial breast irradiation (sPBI) can be safely delivered in early-stage hormone receptor-positive (HR+) breast cancer with delayed time to surgery and high pathologic complete response rates. Objectives To examine the maximum tolerated dose (MTD) of sPBI and to evaluate clinical outcomes, including pathological complete response (pCR), time to surgery, and toxic effects, associated with dose escalation. Design, Setting, and Participants This phase 1 nonrandomized clinical trial of dose escalation enrolled patients with HR+, ERBB2-negative, cN0 invasive breast cancer not requiring chemotherapy from a single academic center between December 2019 and April 2024. Interventions Patients were treated with 30, 34, or 38 Gy using MR-guided linear accelerator (MR-LINAC), robotic radiosurgery, or cobalt stereotactic unit. Patients received endocrine therapy and delayed surgery (<= 12 months). Main Outcomes and Measures The MTD was evaluated using dose-limiting toxicity (DLT), defined as grade 3 or higher toxic effects within 90 days. Additionally, pCR, near pCR (npCR), the association of dose escalation with time to surgery, local control, surgical morbidity, and cosmesis were evaluated. Results A total of 44 patients (median [range] age, 64.5 [44.0-77.0] years) were treated, with 14 (31.8%) receiving 30 Gy (median [IQR] follow-up, 52.0 [28.2-54.5] months), 15 (34.1%) receiving 34 Gy (median [IQR] follow-up, 40.0 [36.5-41.0] months), and 15 (31.4%) receiving 38 Gy (median [IQR] follow-up, 20.0 [17.0-22.0] months). MTD was not reached. pCR rates were 35.7% (5 patients), 46.7% (7 patients), and 66.7% (10 patients), while pCR with npCR rates were 64.3% (9 patients), 93.3% (14 patients), and 93.3% (14 patients), respectively. Local control was 100%, and surgical morbidity was 2.2% (1 of 44 patients). The mean (SD) Ki-67 was 11.3% (6.4%) at diagnosis, and on evaluable residual disease, it was 1.9% (2.0%) (P < .001). A time-to-surgery threshold of 277 days was the optimal cutoff for pCR (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.62-0.91). In patients with surgery more than 9 months after sPBI, pCR rates were 100% (5 of 5 patients), 66.7% (4 of 6 patients), and 64.3% (9 of 14 patients) (P = .40), and combined pCR and npCR rates were 100%, 83.3% (5 patients), and 92.9% (13 patients) (P = .69) for the 30, 34, and 38 Gy groups, respectively. For all patients who received surgery more than 9 months after sPBI, the pCR rate was 72.0% (18 of 25 patients). Longer time to surgery was associated with pCR (odds ratio, 1.02; 95% CI, 1.01-1.03; P = .005), while higher radiation dose was not. Acute toxic effects included 32 grade 1, 3 grade 2 (breast pain and dermatitis), and 1 late grade 3 (wound dehiscence in patient with uncontrolled diabetes) events. Cosmesis remained stable at 36 months. Conclusions and Relevance In this nonrandomized clinical trial, the rate of toxic effects was low, and treatments were tolerable up to 38 Gy. Delaying surgery more than 9 months after sPBI with endocrine therapy was associated with increased pCR and npCR (>90%), while higher doses were not. These findings support further investigation of sPBI as a potential nonsurgical approach for selected patients with early-stage HR+ breast cancers.

Purpose We report the financial toxicity and quality-of-life outcomes of our prospective phase 1 dose-escalation study of 5-fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer. Materials and Methods Women with unifocal in situ or invasive epithelial histologies, clinical stages 0, I, or II with tumor size < 3 cm treated with lumpectomy were enrolled in our phase 1 5-fraction S-PBI dose-escalation trial. Our institutionally generated questionnaire on the “Patient Perspective Cost and Convenience of Care” and the EuroQol 5-Dimension 5-level questionnaire were administered to patients treated at follow-up. Results Between 2010 and 2015, 68 of the 75 patients who enrolled and completed treatment on trial completed at least some component of either the EuroQol 5-Dimension 5-level questionnaire or the “Patient Perspective Cost and Convenience of Care” questionnaire. Nearly all patients reported very high satisfaction with their treatment overall, particularly the shortened length of treatment. Over half of the patients reported some level of financial toxicity (FT) despite a significantly shortened treatment time. Patients who reported any FT were significantly younger than patients with no financial burden of treatment (means 59.2 and 63.7, respectively, P = .03). There was no difference in those who reported any level of FT based on patient race, ethnicity, marital, or employment status. This S-PBI regimen did not significantly affect quality of life over a 4-year follow-up. Conclusions These patient-reported outcomes suggest that the use of accelerated partial breast irradiation may offer low FT rates in breast cancer care, particularly for disadvantaged patient groups.

Abstract Objective(s): To explore the impact of pre-operative single fraction stereotactic ablative partial breast irradiation (SPBI) dose escalation (30, 34, or 38Gy) on toxicity and tumor response for early-stage hormone receptor (HR)+ breast cancer in an interim analysis of an expanded cohort phase I dose escalation study (NCT04040569). Methods: Eligible patients (pts) have < 3 cm, HR+, Her2 -, cN0 invasive breast carcinomas not requiring chemotherapy. Patients are treated on either MR LINAC, robotic radiosurgery, or cobalt stereotactic breast units. Endocrine therapy is started two weeks after SPBI. Surgery is completed 2-12 months after SPBI. The primary objective is to escalate single fraction SPBI to an ablative dose without exceeding maximum tolerable dose (MTD). Secondary endpoints include pathologic complete response (pCR), local control, toxicity, cosmesis, and distant disease-free survival. Near complete response (nCR) is defined as RCB 1 and Miller-Payne 4/5. Dose limiting toxicity (DLT) is defined as grade ≥3 toxicity or any grade 4/5 toxicity attributed to SPBI. Each dose cohort enrolls 7-15 pts. Dose escalation is permitted if 0/7, 2/9, ≤3/12, or ≤4/15 patients experienced a DLT within 90 days of SPBI. MTD is exceeded if more DLTs occur in any cohort. Results: From 12/2019 to 6/2023, 11 and 15 pts were treated with 30Gy and 34Gy, respectively. Rates of pCR/nCR are 37.5% for 30Gy versus 92.8% 34 Gy (p=0.01). At 30Gy, 8/11 pts (73%) underwent surgery with a median 4.3 (range 2.8-5.9) month interval from SPBI to surgery: 0/8 (0%) had a pCR and 3/8 (37.5%) had a nCR. At dose level 34Gy, 14/15 pts (93%) underwent surgery with a median 7.3 (range 5.9-12) month interval from SPBI to surgery: 6/14 (42.8%) had a pCR while 7/14 (50%) had a nCR. Of the 8 pts with a nCR, 50% had only 1-3mm of residual disease. The mean ki67 for the entire cohort was 12.0% +/- 6.9% at diagnosis and decreased to 1.4 +/-2.3% at surgery. 13/14 (92.8%) pts with residual disease had a ki67 < 3% after surgery and SPBI. There were 33 acute grade 1; 2 acute grade 2 (breast pain and dermatitis); and 10 late grade 1 [1 grade 2 (breast pain), and 1 grade 3 (slow healing wound) in an uncontrolled diabetic] toxicities. Conclusion: First study to show pre-operative SPBI up to 34Gy in a single fraction was safe and effective for early-stage HR+ breast cancer. Escalating the dose has achieved a dramatic improvement in pCR/nCR (92.8%) suggesting this is an exciting approach for potentially eliminating tumor with radiation/endocrine therapy alone in early stage breast cancer and potentially paving a path towards non-surgical management in highly selected patients. Citation Format: Asal Rahimi, A Marilyn Leitch, Baṣak Dogan, Prasanna Alluri, Deborah Farr, Mona Arbab, Stephen Seiler, Nathan Kim, Rachel Wooldridge, Nisha Unni, Chika Nwachukwu, Ina Patel, You Zhang, David Parsons, Anvy Nguyen, Howard E Morgan, Heather McArthur, Sunati Sahoo, Robert Timmerman. Early Results of a Phase I Pre-Operative Single Fraction Ablative Trial for Early Stage Breast Cancer [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 PS01-09.

We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using the GammaPodTM stereotactic radiation system.Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity was graded using the NCI version 4.0 and RTOG/EORTC late radiation scale.From 3/2019-10/2021, 74 patients were treated respectively. Of these, 38 were treated to 40Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 24 months (mo), range (r) 3-39mo. Median age was 63 years (r 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. 45/46 invasive tumors were ER+. 60/74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 221 acute grade 1 toxicities, and 28 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (10), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 54 Grade 1 late toxicities, 4 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis (2), and pain (2). Two patients developed grade 1 asymptomatic nonpalpable fat necrosis both diagnosed at 12 months after radiation treatments. The most common grade 1 late toxicities were breast pain (14), hyperpigmentation (8), fibrosis (10), and fatigue (5). Physicians scored cosmesis excellent or good 70/73 (95.8%), 58/60 (96.7%), 36/36 (100%),17/17(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 62/71 (83.7%), 53/59 (89.8%), 33/36 (91.6%), 17/18 (94.4%). There have been no reports of disease recurrences.Results at 24-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Continued analysis of all cohorts is in progress.gov identifier is NCT03581136.