Management of Male Patients With Occult Breast Cancer: Analysis of the National Cancer Database.

INTRODUCTION: Occult breast cancer (OBC) consists of <0.1% of breast cancer cases in the United States. Male occult breast cancer (mOBC) has not been well-studied outside of case reports, and management is largely based on female OBC (fOBC) studies. We aim to examine the prevalence of mOBC among those in the National Cancer Database with breast cancer and describe treatment modalities received by mOBC compared to fOBC. METHODS: The National Cancer Database was queried for patients with OBC from 2004 to 2018. Chi-Square test and Fisher's exact tests compared patient, clinical, and facility characteristics by sex. Treatment modalities [systemic therapy, radiation therapy, axillary lymph node dissection, modified radical mastectomy (MRM)] were compared. A subgroup analysis examined pathologic upstaging in patients who underwent MRM. RESULTS: Of 23,374 male patients with breast cancer, 0.13% were identified to have mOBC [versus 0.09% in fOBC]. cN2/N3 disease was significantly more prevalent in the mOBC cohort (61.3%) than in the fOBC cohort (30.7%, P < 0.001). Receipt of axillary lymph node dissection or MRM was not significantly different by sex. Male OBC (mOBC) patients were less likely to receive trimodality treatment than fOBC patients. In patients who underwent MRM, more mOBC patients [75%] were pathologically upstaged as T+ after mastectomy than fOBC patients [30%, P < 0.001], questioning the adequacy of diagnostic workup for mOBC compared to fOBC. CONCLUSIONS: This review confirms mOBC as an extremely rare disease. Multimodal treatments have been highly utilized to optimize care in this patient population. Further investigation is warranted to examine the survival benefit of treatment regimens for mOBC.

Benefits of Trimodality Therapy Compared with Systemic Therapy Alone in Male Patients with Stage IV Breast Cancer.

BACKGROUND: Male breast cancer (MBC) represents <1% of all breast cancer (BC) diagnoses. Recent publications in female stage IV BC have shown that surgical intervention has a survival benefit. This study aims to determine the impact of surgical intervention in men with stage IV BC and known estrogen (ER) and progesterone receptor (PR) status. METHODS: The National Cancer Database was used to identify 539 stage IV MBC patients with known ER/PR status from 2004 to 2017. Chi-square tests examined subgroup differences between the treatment modalities received. Overall survival (OS) was assessed using the Kaplan-Meier method. Multivariate Cox proportional hazard models examined factors associated with survival. RESULTS: The Kaplan-Meier estimation showed that ER-positive (ER+) and PR-positive (PR+) patients who received surgery, systemic therapy, and radiation (Trimodality) or systemic therapy and surgery (ST+Surg) had improved survival compared with systemic therapy alone (ST) [ER+, p < 0.003; PR+, p < 0.033]. For ER+ patients, the 5-year OS rates by treatment were: Trimodality, 40%; ST+Surg, 27%; and ST, 20%. For PR+ patients, the 5-year OS rates were: Trimodality, 39%; ST+Surg, 24%; and ST, 20%. The Cox proportional hazard model revealed a survival advantage in patients who received Trimodality compared with ST (hazard ratio 0.622; p < 0.002). The timing of systemic therapy in relation to surgery was not found to be significant. CONCLUSIONS: Trimodality therapy has a survival benefit in stage IV MBC patients with known ER+ status than in male patients who receive systemic therapy alone.

Insurance Status and Travel Distance to Single Treatment Facility Predictive of Mastectomy.

BACKGROUND: We evaluated the impact of insurance status and travel distance on the receipt of total mastectomy without reconstruction (TM) compared to breast conserving surgery with radiation (BCT) for early-stage breast cancer (BC) patients who received care at a single facility. We hypothesized that, lack of insurance and increased travel distance would be predictive of TM over BCT and disparities would vary by different races and/or ethnicities. METHODS: Using the National Cancer Database from 2010-2017, we examined surgical patients with stage I or II BC, who received care at one facility. Chi-square tests examined subgroup differences by BCT or TM. Multivariable logistic regressions evaluated patient, facility, and pathologic factors associated with the receipt of TM over BCT for the entire cohort and by races and/or ethnicities. RESULTS: Of the 284,202 patients, 70.1% received BCT while 29.9% received TM. After adjustment travel distance > 60 miles to a treatment facility, and non-insured patients were more likely to receive TM over BCT, when compared to travel distance < 20 miles and private insurance (all P < 0.05). Compared to other races and/or ethnicities, African Americans traveling > 60 miles were 65.4% more likely to receive TM over BCT compared to those traveling < 20 miles (P < .0001). Across all races and/or ethnicities after adjustment, lack of insurance was predictive for receipt of TM over BCT (P < 0.05). CONCLUSIONS: Despite treatment at one facility, increased travel distance and insurance status are independently predictive of the receipt of TM over BCT in patients with early-stage BC. While travel distance is particularly impactful for African Americans, the impact of not having insurance on surgical treatments is universal across all races and/or ethnicities.

The role of physical arm function and demographic disparities in breast cancer survivors' ability to return to work.

PURPOSE: Ability to return to work (RTW) is an important aspect of breast cancer that is limited for many survivors. With 90% survivorship in the USA, it is imperative that focus shifts toward the improvement of physical arm function to improve survivors' ability to RTW. This narrative review discusses the role of physical arm function and demographic disparities in breast cancer survivor RTW. METHODS: Literature on physical function, arm function, and demographic disparities following breast cancer treatment and their implications for RTW is discussed. RESULTS: The ability to RTW is a key component of recovery for breast cancer survivors, but challenges and inequalities persist. Treatment effects can induce and prolong functional disability, affecting survivors' ability to RTW. These effects may be compounded for survivors whose occupation requires physical arm function. The RTW landscape, including the occupations survivors have, the physical function required for job tasks, and availability of workplace accommodations, is also unclear. Additional demographic disparities (e.g., income, live in rural area) exist, but the extent to which these factors influence RTW is not well understood. More work is needed to understand the compounded impact of treatment effects, demographic disparities, and occupational factors on RTW. Multidisciplinary rehabilitation that includes occupational counseling and exercise is a promising approach, but widespread adoption in the US healthcare model presents an ongoing challenge. Areas for further research are highlighted. CONCLUSION: There is an incomplete understanding of the effects of treatment on physical arm function and the role of demographic disparities on breast cancer survivor RTW.

Benefits of Surgical Treatment of Stage IV Breast Cancer for Patients With Known Hormone Receptor and HER2 Status.

BACKGROUND: For the 6% of breast cancer patients with a diagnosis of stage IV disease, systemic therapy is the cornerstone of treatment, with an unclear role for surgery. Limited evidence exists to delineate treatment methods with regard to hormone receptor and human epidermal growth factor receptor 2 (HER2) status. METHODS: The National Cancer Database was used to identify 12,838 stage IV breast cancer patients with known hormone receptor and HER2 status from 2010 to 2015. Chi square tests examined subgroup differences between the treatment methods received. Using the Kaplan-Meier method, 5-year overall survival (OS) was assessed. Multivariate Cox proportional hazard models examined factors associated with survival. RESULTS: A survival advantage was noted for patients who received either systemic therapy and surgery (ST + Surg: hazard ratio [HR] 0.723; 95% confidence interval [CI] 0.671-0.779) or systemic therapy, surgery, and radiation (Trimodality: HR 0.640; 95% CI 0.591-0.694) (both p < 0.0001) compared with systemic therapy alone (ST). The HER2+ patients who received Trimodality or ST + Surg had a better 5-year OS rate than those who received ST (Trimodality [48%], ST + Surg [41%], ST [29%]; p < 0.0001). The sequence of chemotherapy in relation to surgery is significant, with the greatest survival advantage noted for recipients of neoadjuvant chemotherapy (NAC) compared with patients who had adjuvant chemotherapy when they had positive hormone receptor and HER2 status (HER2 + NAC: HR 0.477; estrogen receptor-positive [ER+] NAC: HR 0.453; progesterone receptor-positive [PR+] NAC: HR 0.448; all p < 0.0001). CONCLUSIONS: Surgery in addition to ST has a survival benefit for stage IV breast cancer patients with known hormone receptor and HER2 status and should be considered after NAC for patients with ER+, PR+, or HER2+ disease.

Prolonged Opioid Use After Surgery for Early-Stage Breast Cancer.

INTRODUCTION: This study examined the patterns of prolonged opioid use and the factors associated with higher risk of prolonged opioid use among opioid-naïve working-age patients with early-stage breast cancer. METHODS: Using MarketScan data, the study identified 23,440 opioid-naïve patients who received surgery for breast cancer between January 2000 and December 2014 and filled at least one opioid prescription attributable to surgery. Prolonged opioid use was defined as one or more prescriptions for opioids within 90 to 180 days after surgery and defined extra-prolonged opioid use as one or more opioid prescriptions between 181 and 365 days after surgery. Multivariable logistic regressions were performed to ascertain factors associated with prolonged and extra-prolonged use of opioids. FINDINGS: Of the 23,440 patients, 4,233 (18%) had prolonged opioid use, and 2,052 (9%) had extra-prolonged opioid use. Patients who received mastectomy plus reconstruction had the highest rate of prolonged opioid use (38%) followed by mastectomy alone (15%). A multivariable logistic regression confirmed that patients with mastectomy and reconstruction had the highest odds ratio of prolonged opioid use compared to lumpectomy and whole breast irradiation (adjusted odds ratio, 5.6; 95% confidence interval, 5.1-6.1). Mean daily opioid dose was consistently high without any obvious dosage reduction among patients with opioid use. INTERPRETATION: This large observational study showed a high rate of prolonged opioid use among patients who received surgery for early-stage breast cancer and found significant difference in prolonged opioid use by treatment type. IMPLICATIONS FOR PRACTICE: This large observational study found a high rate of prolonged opioid use among working-age patients with early-stage breast cancer who received curative surgery, especially among patients who received mastectomy. Among patients with opioid use, the mean daily opioid dose was consistently high without any obvious dosage tapering. This study highlights the need to emphasize appropriate opioid therapy and potential dosage reduction or discontinuation among patients with early-stage breast cancer who received surgical interventions.

The influence of mastectomy and reconstruction on residual upper limb function in breast cancer survivors.

PURPOSE: Breast cancer survivorship is common (90% of women survive 5 or more years), but many women are not able to return to full function and well-being after treatment due to functional limitations, persistent pain, and inability to perform daily activities. Since each surgical reconstructive option (e.g., autologous tissue flaps versus implants) can impact shoulder and arm function differently, it is important to understand how shoulder and upper limb strength, mobility, and function are influenced by the type of surgical intervention. Efforts can then focus on prehabiliation strategies to prevent the onset of limitations and on developing rehabilitation protocols that directly target shortcomings. METHODS: The current paper presents a review summarizing how shoulder and upper limb function may be affected by surgical mastectomy and breast reconstruction. RESULTS: Mastectomy and breast reconstruction with implants or autologous tissues present different functional outcomes for patients. Each surgical procedure is associated with unique sequelae derived from the tissues and procedures associated with each surgery. Characterizing the specific functional outcomes associated with each surgical approach will promote the development of targeted rehabilitation strategies that can be implemented into a multidisciplinary treatment planning pathway for breast cancer patients. CONCLUSIONS: Surgical treatments for breast cancer, including mastectomy and breast reconstruction, can have negative effects. Focused efforts are needed to better understand treatment-specific effects so that targeted rehabilitation can be developed to improve patient function, QoL, and ability to return to work and life activities post-breast cancer.

Excision recommended in high-risk patients: Revisiting the diagnosis of papilloma on core biopsy in the context of patient risk.

We investigate the clinical history, past medical history, and risk status in women with benign intraductal papillomas(IDP). We observed an upgrade rate of 3.9% to ductal carcinoma in situ (DCIS) and upgrade rate of 10.7% to a high-risk lesion. Prior or concurrent atypia or cancer and high-risk status had a significant increase risk of upgrade. Surgical excision of papillomas is recommended especially in high-risk patients and women with concurrent or history of atypia or malignancy.

Should we excise? Are there any clinical or histologic features that predict upgrade in papillomas, incidental or non-incidental?

The clinical decision to excise intraductal papilloma (IDP) without atypia diagnosed on biopsy remains controversial. We sought to establish clinical and histologic predictors (if any) which may predict upgrade in IDP. 296 biopsies (in 278 women) with histologic diagnosis of IDP without atypia were retrospectively identified and placed into Incidental (no corresponding imaging correlate), or Non-incidental (positive imaging correlate) groups. 253/296 (85.5%) cases were non-incidental, and 43/296 (14.5%) were incidental. 73.1% (185/253) non-incidental and 48.8% (21/43) incidental cases underwent excision. 12.4% (23/185) non-incidental cases underwent an upgrade to cancer or high-risk lesion; namely 8-Ductal carcinoma in situ (DCIS), 8-atypical ductal hyperplasia (ADH), 6-lobular neoplasia, and 1-flat epithelial atypia. There was no histopathologic feature on the biopsy in the non-incidental group which predicted upgrade; however a past history of atypia was significantly associated with upgrade. 2 of the 21 incidental cases upgraded (1 to ADH and 1 to lobular neoplasia); the former had a past history of ADH. Both incidental upgrades were >1 mm in size, and were not completely excised on the biopsy. None of the incidental cases which appeared completely excised on biopsy upgraded, irrespective of the size on biopsy. These findings suggest that all non-incidental IDPs should be considered candidates for surgical excision, given the 12.4% upgrade rate and no definitive histologic predictors of upgrade. Patients with incidental IDPs (if <1 mm, completely excised on biopsy and with no history of high risk breast lesion) can be spared excision.

Preserving choice in breast cancer treatment: A different perspective on contralateral prophylactic mastectomy.

Contralateral prophylactic mastectomy is the removal of both breasts when only one is affected by cancer. Rates of this controversial cancer treatment have been increasing since the late 1990s, even among women who do not have the kind of family history or known genetic mutation that would put them at high-risk for another breast cancer. Citing contralateral prophylactic mastectomy's lack of oncologic benefit and increased risk of surgical complications, the American Society of Breast Surgeons discourages contralateral prophylactic mastectomy for average-risk women with unilateral cancer, as does most of the medical literature on this topic. Within this literature, desire for contralateral prophylactic mastectomy is often painted as the product of an emotional overreaction to a cancer diagnosis and misunderstanding of breast cancer risk. Drawing on the personal experience of a breast cancer survivor, as well as relevant medical literature on breast cancer screening and surgery, this article offers a different perspective on the ongoing popularity of contralateral prophylactic mastectomy, one that focuses on practical experiences and logical deliberations about those experiences. Specifically, it calls attention to two features of the contralateral prophylactic mastectomy decision-making situation that have been inadequately covered in the medical literature: (1) the way that breast cancer screening after a breast cancer diagnosis can become a kind of radiological overtreatment, even for "average-risk" women; and (2) how desire for bodily symmetry after breast cancer, which can best be achieved through bilateral reconstruction or no reconstruction, drives interest in contralateral prophylactic mastectomy. The goal of this article is not to suggest that all women who want contralateral prophylactic mastectomy should have the surgery. In some cases, it is not advisable. But many "average-risk" women with unilateral cancer have good reasons for wanting contralateral prophylactic mastectomy, and we believe their right to choose it should be protected.

Endocrine therapy initiation and overall survival outcomes with omission of radiation therapy in older Medicare patients with early-stage hormone-receptor-positive breast cancer.

BACKGROUND: Guidelines allow for the omission of radiotherapy in older women with early-stage, hormone-receptor-positive breast cancer, given that the patients receive adequate endocrine therapy (ET). However, the initiation of ET and survival outcomes after forgoing radiation therapy among these patients have not been well-studied. METHODS: We identified patients aged 70 to 90 years old newly diagnosed in 2010-2015 with early-stage, hormone receptor positive, and human epidermal growth factor receptor 2 (HER2) negative (HR+/Her2-) breast cancer who received lumpectomy and omitted radiation therapy using the SEER-Medicare database. We examined the initiation of ET and the utilization patterns of ET using a multivariable logistic regression. We further examined the overall survival outcomes using Kaplan-Meier estimation and Cox proportional hazard model with inverse probability weighting. RESULTS: Of the 2618 patients, 808 (30.9%) received no ET. The multivariable logistic regression showed that more recent years had better ET initiation (2013-2015 vs. 2010-2012: OR = 1.39, 95% CI:[1.16, 1.66]), while older patients (81-90 vs. 70-80: OR = 0.45, 95% CI:[0.38, 0.54]) were less likely to receive ET. Both the Kaplan-Meier estimation (log-rank p-value<0.0001) and the Cox proportional hazard model with inverse probability weighting (HR = 0.76, 95% CI:[0.58, 0.99]) showed that receiving ET was associated with better overall survival. CONCLUSION: This population-based study suggests that a sizable proportion of patients who omitted radiation did not receive endocrine therapy and receiving endocrine therapy was beneficial among these patients. Although ET initiation has improved in more recent years, certain patient groups were still especially susceptible to no endocrine therapy.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery.

BACKGROUND: Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)

Utilization of Mammography During the Last Year of Life Among Older Breast Cancer Survivors.

Background: Mammography is generally recommended for breast cancer survivors. However, discussion is ongoing about stopping surveillance mammography when life expectancy is <5-10 years as the benefit of screening might be diminished toward the end of life. The utilization pattern of mammography in the last year of life among this population has not been well studied. Methods: We identified 58,736 females diagnosed with breast cancer between January 2002 and December 2015, who died at the age of at least 67, from the SEER-Medicare database. We examined the utilization patterns of mammography during their last year of life and investigated factors associated with the use of mammography at the end of life using a multivariable logistic regression model. Results: Overall, 28.5% of the patients received mammography during the last year of life. Multivariable logistic regression showed that older age (OR = 0.31, 95% CI = 0.29-0.34, p < 0.001 for 95 vs. 85 years old), more advanced cancer stage (OR = 0.22, 95% CI = 0.20-0.24 p < 0.001 for distant vs. localized disease), and higher comorbidity score (OR = 0.92, 95% CI = 0.91-0.93, p < 0.001 for every 1-point increase) were associated with less mammography use. Age was nonlinearly associated with mammography use, with a steady proportion of patients receiving a mammography until approximately age 80 and then a sharp decrease thereafter. Conclusion: This population-based study found that a sizable proportion of older breast cancer survivors received mammography during the last year of life.

Review of Variables Associated With Positive Surgical Margins Using Scout Reflector Localizations for Breast Conservation Therapy.

OBJECTIVE: To evaluate factors contributing to positive surgical margins associated with reflector guidance for patients undergoing breast conserving therapy for malignancy. MATERIALS AND METHODS: A retrospective IRB-approved review of our institutional database was performed for malignant breast lesions preoperatively localized from January 1, 2018 to December 31, 2020. The following data was recorded using electronic medical records: lesion type and grade, lesion location, reflector and wire placement modality, use of intraoperative ultrasound, margin status, patient age, family history, BMI, and final pathology. Statistical analysis was performed with univariate summary statistics and logistic regression. P < .05 was significant. RESULTS: A total of 606 image-guided pre-surgical localizations were performed for lumpectomies of breast malignancies. A total of 352 of 606 (58%) wire localizations and 254 of 606 (42%) SCOUT reflector localizations were performed. Sixty out of 352 (17%) of wire-localized patients had positive surgical margins, whereas forty-eight out of 254 (19%) of reflector-localized patients had positive surgical margins. (OR = 1.12, P value: .59). For reflector guided cases, the use of intraoperative ultrasound (IOUS) was associated with decreased positive margin status (OR = 0 .28, 95% CI = [0.14, 0.58]) while in situ disease was associated with increased positive margin status (OR = 1.99, 95% CI = [1.05, 3.75]). No association between modality used for localization (mammography vs. ultrasound) and positive margin status was observed (OR = 0.63, 95% CI = [0.33, 1.19]). No association between positive margins and age, family history, tumor location and BMI was observed. CONCLUSION: For reflector guided surgeries, the use of IOUS was associated with decreased positive margins, by contrast the presence of ductal carcinoma in situ was associated with increased positive margins. There was no statistically significant difference in surgical outcomes for reflector-guided localization compared to wire localizations of the breast.

Creation of a Human Factors Board to Support Well-Being in General Surgery Residents.

PROBLEM: Demands placed on resident physicians can make it difficult to keep up with personal needs, often affecting well-being. For military pilots, confidential and nonpunitive human factors boards (HFBs) identify pilots' human factors (personal or professional problems that might interfere with the ability to perform effectively) and make recommendations for support. The authors sought to determine the feasibility of establishing an HFB for resident physicians and its utility for general surgery residents. APPROACH: Publicly available information on HFBs was reviewed and translated to the structure of a general surgery residency. An HFB consisting of a faculty member, resident representative, and neutral third party was established for the general surgery residency program (consisting of 42 residents during the study period) at Penn State Health. From January 1 to July 1, 2020, the HFB responded to human factors needs of general surgery residents. Residents could make requests for themselves or another resident. If all HFB members were in agreement that a request was reasonable, the appropriate resource was directed to the requesting resident and funding was disbursed (if applicable) by the third party. OUTCOMES: From January 1 to July 1, 2020, 14 requests were made. Of these, 3 (21%) were made for another resident and 12 (86%) were fulfilled through resources arranged by the HFB. All requests occurred between January 1 and April 1, 2020, likely because of the COVID-19 pandemic. The overall cost of the program was $932.80. NEXT STEPS: The HFB represents an adaptable tool that can meet residents' specific needs as they arise and a mechanism through which residents can receive a tangible response to human factors. Formal feedback is needed to identify areas that could be improved. This structure could be generalized to other graduate medical education programs and physicians at all levels.

Breast Cancer Survival in Eastern Region of Ghana.

Objective: Five-year overall survival rate of breast cancer in low-income countries (LICs) is significantly lower than in high-resource countries. This study explored clinical and pathological factors influencing mortality in the Eastern region of Ghana. Methods: We performed a retrospective medical chart review for patients undergoing surgery and chemotherapy for breast cancer at a regional hospital in Ghana from January 2014 to January 2017. Descriptive and survival analysis was done. Results: One hundred and twenty-nine patients were included in the study. The median age at presentation was 51 years. Sixty percent of patients presented with poorly differential histological grade III. The most common histological type was invasive ductal carcinoma (83%). Based on stage assessment using only tumor size and lymph node status, 60% presented at stage 3. Only 25% were tested for hormone receptor proteins and HER2 status. Of these, 57% had triple-negative breast cancer (TNBC). The 3-year overall survival rate was only 52%. Conclusion: The cumulative 3-year survival was 52%. Despite success in reducing cancer mortality in northern Africa, survival in sub-Saharan Africa remains poor. A significantly higher percentage of GIII and TNBC is found in breast cancers seen in Ghana. When combined with limited capacity for accurate diagnosis, cancer subtype analysis, adequate therapy, and follow-up, late-stage presentation leads to poor outcomes. Future studies should emphasize the identification of barriers to care and opportunities for cost-effective and sustainable improvements in diagnosing and treating breast cancer in LICs.

Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence-Guided System: A Nonrandomized Controlled Trial.

Importance: Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time. Objective: To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS. Design, Setting, and Participants: This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021. Interventions: Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins. Main Outcomes and Measures: Adverse events and sensitivity, specificity, and reexcision rate. Results: Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%). Conclusions and Relevance: In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial. Trial Registration: ClinicalTrials.gov Identifier: NCT03321929.