The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study.

BACKGROUND: Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival. METHODS: In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20). RESULTS: Ex vivo cytokine production capacity of TNF, IL-6 and IL-1ß was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1ß after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1ß and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively). CONCLUSIONS: This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

Ethnic inequities in use of breast conserving surgery and radiation therapy in Aotearoa/New Zealand: which factors contribute?

PURPOSE: Aotearoa/New Zealand (NZ) faces ethnic inequities with respect to breast cancer survival and treatment. This study establishes if there are ethnic differences in (i) type of surgery and (ii) receipt of radiotherapy (RT) following breast conserving surgery (BCS), among women with early-stage breast cancer in NZ. METHODS: This analysis used Te Rehita Mata Utaetae (Breast Cancer Foundation National Register), a prospectively maintained database of breast cancers from 2000 to 2020. Logistic regression models evaluated ethnic differences in type of surgery (mastectomy or BCS) and receipt of RT with sequential adjustment for potential contributing factors. Subgroup analyses by treatment facility type were undertaken. RESULTS: Of the 16,228 women included, 74% were NZ European (NZE), 10.3% were Maori, 9.4% were Asian and 6.2% were Pacific. Over one-third of women with BCS-eligible tumours received mastectomy. Asian women were more likely to receive mastectomy than NZE (OR 1.62; 95% CI 1.39, 1.90) as were wahine Maori in the public system (OR 1.21; 95% CI 1.02, 1.44) but not in the private system (OR 0.78; 95% CI 0.51, 1.21). In women undergoing BCS, compared to NZE, Pacific women overall and wahine Maori in the private system were, respectively, 36 and 38% less likely to receive RT (respective OR 0.64; 95% CI 0.50, 0.83 and 0.62; 95% CI 0.39, 0.98). CONCLUSION: A significant proportion of women with early-stage breast cancer underwent mastectomy and significant ethnic inequities exist. Recently developed NZ Quality Performance Indicators strongly encourage breast conservation and should facilitate more standardized and equitable surgical management of early-stage breast cancer.

Comparison of long-term oncologic outcomes of central lumpectomy and conventional breast-conserving surgery for invasive breast cancer: propensity score matching analysis.

PURPOSE: Central lumpectomy (CL) is a breast-conserving surgical (BCS) technique that involves excision of the nipple-areolar complex with breast tumor in centrally located breast cancers. We aimed to investigate the long-term clinical outcomes of CL in comparison with conventional BCS (cBCS). METHODS: Patient records who underwent BCS with clear resection margins for invasive breast cancer between 2004 and 2018 were retrospectively reviewed. Of the total 6,533 patients, 106 (1.6%) underwent CL. Median follow-up duration was 73.4 months. 1:3 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize selection bias. RESULTS: The CL group showed a significantly higher ipsilateral breast tumor recurrence (IBTR) rate than the cBCS group (10-year IBTR rate: 5.8% vs. 3.1%, p = 0.004), even after adjusting for other variables (hazard ratio (HR), 2.65; 95% confidence interval (CI), 1.07-6.60, p = 0.048). However, there were no significant differences observed in regional recurrence, distant metastasis, or overall survival rates between the two groups. Both PSM and IPTW analyses showed significantly higher IBTR in the CL group (PSM HR, 3.27; 95% CI, 0.94-11.36; p = 0.048 and IPTW HR, 4.66; 95%CI, 1.85-11.77; p < 0.001). Lastly, when analyzing 2,213 patients whose tumors were located within 3 cm of the nipple, the CL group showed a significantly higher IBTR than the cBCS group before and after PSM. CONCLUSION: CL was associated with a higher rate of IBTR compared to cBCS, while other survival outcomes were comparable. For centrally located tumors, CL may be considered for patients preferring breast preservation. However, higher risk for IBTR should be informed and careful surveillance may be necessary during the early post-operative follow-up periods.

Quantitative assessment of breast volume changes after whole-breast irradiation for breast cancer using breast auto-segmentation.

PURPOSE: This study aimed to quantitatively estimate the changes in breast volume associated with radiotherapy in patients undergoing breast-conserving surgery and whole-breast irradiation (WBI). METHODS: Pre-WBI simulation computed tomography (CT) scans and post-WBI follow-up chest CT scans from a total of 1,151 breast cancer patients were analyzed using a deep-learning-driven auto-segmentation approach. The CT-based asymmetry index (CTAI) was calculated by dividing the volume of the irradiated breast by the volume of the contralateral breast. Significant breast shrinkage was defined as a CTAI < 0.85. To quantify changes in CTAI over the follow-up period, the CTAI ratio was determined as the post-WBI CTAI divided by the pre-WBI CTAI. A multivariate logistic regression analysis was conducted to identify potential variables associated with post-WBI significant breast shrinkage. RESULTS: The median CTAI values for pre- and post-WBI CT scans were 0.973 (interquartile range: 0.887-1.069) and 0.866 (interquartile range: 0.773-0.967), respectively. The difference between them was statistically significant (p < 0.001). Following WBI, there was an increase in the rate of significant breast shrinkage from 16.3 to 44.8%. The CTAI ratio showed a negative association with the time interval (p < 0.001, Pearson r = - 0.310). In the multivariate logistic regression analysis, lower pre-WBI CTAI, younger age, and longer interval between CT scans were found to be significantly associated with a higher occurrence of post-WBI significant breast shrinkage. CONCLUSION: Breast volume decreases following WBI, and this decrease is correlated with an increased duration after WBI. These findings highlight the long-term consequences of WBI on breast asymmetry.

Surgical marker navigation system in breast conserving surgery and excision of non-palpable lesions: first Spanish single-center experience.

BACKGROUND: Due to the establishment of screening mammography for breast cancer detection, the number of non-palpable lesions has increased. Thus, an optimal localization system is mandatory for the excision of non-palpable breast tumors. OBJECTIVE: The aim of the study is to report the feasibility Surgical Marker Navigation (SMN) system Sirius Pintuition® for the excision of non-palpable breast tumors and non-palpable axillary lymph nodes. METHODS: A retrospective observational study of patients undergoing breast-conserving surgery and lymph node excision guided by SMN between December 2022 and May 2023 was performed. RESULTS: A total of 84 patients underwent excision of non-palpable breast tumors (77; 91.7%) or non-palpable axillary lymph-nodes (7; 8.3%) using SMN. In total, 94 markers were placed, in 74 patients (88.1%) only one marker was placed, whereas in 10 patients (11.9%) two markers were placed to correctly localize the lesion in the operating room. Most markers were placed using ultrasonographic guidance (69; 82.1%). Seventy-seven patients underwent breast-conserving surgery (91.7%) and 7 (8.3%) lymph node excision. In 10 cases (11.9%), the marker was accidentally displaced during surgery due to the use of magnetized instruments, although the specimen could be removed. In sum, all the markers were removed from the patients, although the marker retrieval rate, as we defined it (percentage of patients in whom the initial excised specimen contained the marker divided by the total number of patients), was 88.1%. CONCLUSION: The use of Sirius Pintuition® SMN for non-palpable breast tumors and non-palpable lymph nodes is feasible, with a retrieval rate of 88.1%.

Neoadjuvant endocrine treatment in hormone receptor-positive breast cancer: Does it result in more breast-conserving surgery?

BACKGROUND: Patients with locally advanced endocrine positive tumors who will not benefit from chemotherapy can be treated by either primary surgery or neoadjuvant endocrine therapy (NET). How often does NET result in breast-conserving surgery (BCS)? METHODS: We conducted a literature search in PubMed and Embase, to identify articles on surgical treatment after NET. RESULTS: In 19 studies the pathological complete response (pCR) rate was reported after NET; an overall pCR rate of 1% was found. Compared with neoadjuvant chemotherapy (NCT), the BCS rate was significantly higher after NET (OR 0.60; 95% CI, 0.51-0.69; P < 0.00001). The surgical conversion rate was reported in eight studies [4-75.9%], with a mean of 30.2%. CONCLUSION: This review found that one out of three patients becomes eligible for BCS after treatment with NET.

Comparison of long-term oncological outcomes after central lumpectomy versus nipple-sparing breast-conserving surgery for centrally located breast cancer: a propensity score-matched study.

PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.

Breast surgery after neoadjuvant chemotherapy in patients with lobular carcinoma: surgical and oncologic outcome.

INTRODUCTION: Breast cancer patients with invasive lobular carcinoma (ILC) have an increased risk of positive margins after surgery and often show little response to neoadjuvant chemotherapy (NAC). We aimed to investigate surgical outcomes in patients with ILC treated with NAC. METHODS: In this retrospective cohort study, all breast cancer patients with ILC treated with NAC who underwent surgery at the Netherlands Cancer Institute from 2010 to 2019 were selected. Patients with mixed type ILC in pre-NAC biopsies were excluded if the lobular component was not confirmed in the surgical specimen. Main outcomes were tumor-positive margins and re-excision rate. Associations between baseline characteristics and tumor-positive margins were assessed, as were complications, locoregional recurrence rate (LRR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: We included 191 patients. After NAC, 107 (56%) patients had breast conserving surgery (BCS) and 84 (44%) patients underwent mastectomy. Tumor-positive margins were observed in 67 (35%) patients. Fifty five (51%) had BCS and 12 (14%) underwent mastectomy (p value < 0.001). Re-excision was performed in 35 (33%) patients with BCS and in 4 (5%) patients with mastectomy. Definitive surgery was mastectomy in 107 (56%) patients and BCS in 84 (44%) patients. Tumor-positive margins were associated with cT ≥ 3 status (OR 4.62, 95% CI 1.26-16.98, p value 0.021) in the BCS group. Five-year LRR (4.7%), RFS (81%), and OS (93%) were not affected by type of surgery after NAC. CONCLUSION: Although 33% of ILC breast cancer patients undergoing BCS after NAC required re-excision for positive resection margins, it is considered safe given that five-year RFS remained excellent and LRR and OS did not differ by extent of surgery.

Addressing radiotherapy-induced fibrosis: the potential of platelet-rich plasma and infliximab for improved breast cancer management.

Breast cancer treatment encompasses various therapeutic modalities, including surgery, radiotherapy, and chemotherapy. Breast-conserving surgery has been an integral part of breast cancer management. However, radiotherapy, an important component of breast cancer management, can lead to complications, particularly fibrosis, affecting reconstructive surgery outcomes. We conducted an in vivo study using 48 female Wistar Albino rats, employing segmental mastectomy and radiotherapy to simulate post-mastectomy conditions. The rats were divided into six groups: control, mastectomy, mastectomy + radiotherapy, mastectomy + platelet-rich plasma (PRP) + radiotherapy, mastectomy + infliximab + radiotherapy, and mastectomy + infliximab + PRP + radiotherapy. Edema, hyperemia, inflammation, and fibrosis were assessed as indicators of tissue response. Histopathological analysis revealed that mastectomy + infliximab and mastectomy + infliximab + PRP groups showed significant reductions in fibrosis compared to other groups. Edema, hyperemia, and inflammation were also less severe in these groups compared to the control group. Radiotherapy-induced fibrosis is a major concern in breast reconstruction. Our study suggests that local PRP application and systemic infliximab administration, either alone or in combination, could mitigate the adverse effects of radiotherapy. This approach has the potential to improve reconstructive outcomes in patients undergoing or having the possibility to undergo radiotherapy. This is the first study showing the effectiveness of infliximab and PRP combination on wound healing. The provided experimental rat model might offer guidance for further research. This study provides insights into optimizing outcomes in reconstructive breast surgery, paving the way for further research and clinical studies.

Clinicopathological Predictors of Positive Resection Margins in Breast-Conserving Surgery.

BACKGROUND: Ductal carcinoma in situ (DCIS) is associated with risk of positive resection margins following breast-conserving surgery (BCS) and subsequent reoperation. Prior reports grossly underestimate the risk of margin positivity with IBC containing a DCIS component (IBC + DCIS) due to patient-level rather than margin-level analysis. OBJECTIVE: The aim of this study was to delineate the relative risk of IBC + DCIS compared with pure IBC (without a DCIS component) on margin positivity through detailed margin-level interrogation. METHODS: A single institution, retrospective, observational cohort study was conducted in which pathology databases were evaluated to identify patients who underwent BCS over 5 years (2014-2019). Margin-level interrogation included granular detail into the extent, pathological subtype and grade of disease at each resection margin. Predictors of a positive margin were computed using multivariate regression analysis. RESULTS: Clinicopathological details were examined from 5454 margins from 909 women. The relative risk of a positive margin with IBC + DCIS versus pure IBC was 8.76 (95% confidence interval [CI] 6.64-11.56) applying UK Association of Breast Surgery guidelines, and 8.44 (95% CI 6.57-10.84) applying the Society of Surgical Oncology/American Society for Radiation Oncology guidelines. Independent predictors of margin positivity included younger patient age (0.033, 95% CI 0.006-0.060), lower specimen weight (0.045, 95% CI 0.020-0.069), multifocality (0.256, 95% CI 0.137-0.376), lymphovascular invasion (0.138, 95% CI 0.068-0.208) and comedonecrosis (0.113, 95% CI 0.040-0.185). CONCLUSIONS: Compared with pure IBC, the relative risk of a positive margin with IBC + DCIS is approximately ninefold, significantly higher than prior estimates. This margin-level methodology is believed to represent the impact of DCIS more accurately on margin positivity in IBC.

Breast Conservation Project: Clinical Outcomes of Extreme Oncoplastic Breast-Conserving Therapy Versus Mastectomy for Large and Multiple Lesions.

INTRODUCTION: Patients with multiple or large malignant breast lesions are classically considered mastectomy candidates, but extreme oncoplastic breast-conservation surgery (eOBCS) has become an alternative approach. There is a paucity of outcomes data comparing eOBCS with mastectomy. METHODS: We reviewed our prospectively maintained, single-institution database. We included patients with non-metastatic breast cancer with multiple ipsilateral or single large (≥ 5 cm) malignant breast lesions identified preoperatively who underwent either eOBCS or mastectomy. Patient demographics, clinicopathologic features, and surgical, oncologic, and cosmetic outcomes were evaluated. RESULTS: Seventy-six (88%) patients underwent eOBCS and 10 (12%) underwent mastectomy. Median follow-up was 24.8 months. Mastectomy patients had larger lesions than eOBCS patients (median 70 mm vs. 32.5 mm; p = 0.06). Six (60%) index mastectomy patients underwent at least one additional surgery. For eOBCS patients, 34 (44%) required re-excision, 7 of whom underwent more than one subsequent surgery to obtain negative margins, and 6 (7.9%) ultimately underwent mastectomy. For patients undergoing additional surgery (n = 40), median time between index and final operation was 315 days for mastectomy versus 21 days for eOBCS patients (p < 0.001). Mastectomy patients more frequently experienced complications (p = 0.001) and underwent cosmetic revision (p < 0.001). There was no difference in cosmetic scores, and eOBCS patients reported less pain (p = 0.009). There were two local and three distant recurrences in the eOBCS cohort and one distant recurrence in the mastectomy group. CONCLUSION: Breast conservation was attainable in over 90% of eOBCS patients. Increased postoperative complications and discomfort and longer duration of surgical treatment in mastectomy patients without oncologic superiority should drive informed patient discussions.

Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Mastectomy has been the standard surgical treatment for ipsilateral breast tumor recurrence (IBTR). Recently, there has been growing interest in repeat breast-conserving surgery (rBCS) for IBTR among breast surgeons; however, there is currently little information regarding patient preferences for surgical procedure for IBTR. The purpose of this study was to evaluate preference for surgical procedure (mastectomy vs. rBCS) among breast cancer patients who had undergone salvage surgery for IBTR. METHODS: Overall, 100 breast cancer patients who had undergone salvage surgery for IBTR were asked about their preferred surgical methods for IBTR and the reason. The association of patient preference and the reasons related to various clinical and pathological factors were assessed. RESULTS: Of the 100 respondents, only 11 patients (11%) preferred rBCS. Patients who had undergone rBCS and radiotherapy for IBTR were significantly more likely to prefer to undergo rBCS than other groups (p = 0.030). The most frequent reason for choosing rBCS was the patient's desire to minimize breast deformity and surgical wounds. CONCLUSIONS: Our study revealed that there is a low rate of patients who opt to undergo rBCS among patients who had undergone salvage surgery for IBTR. Discrepancies in perceptions regarding the surgical procedure for IBTR between patients and their surgeons may exist.

Comparing Costs: Does Extreme Oncoplastic Breast-Conserving Surgery Confer a Cost Benefit When Compared with Mastectomy and Reconstruction?

INTRODUCTION: Extreme oncoplastic breast-conserving surgery (eOBCS) describes the application of OBCS to patients who would otherwise need a mastectomy, and its safety has been previously described. OBJECTIVE: We aimed to compare the costs of eOBCS and mastectomy. METHODS: We reviewed our institutional database to identify breast cancer patients treated surgically from 2018 to 2023. We included patients with a large disease span (≥5 cm) and multifocal/multicentric disease. Patients were grouped by their surgical approach, i.e. eOBCS or mastectomy. The direct costs of care were determined and compared; however, indirect costs were not included. RESULTS: Eighty-six patients met the inclusion criteria, 10 (11.6%) of whom underwent mastectomy and 76 (88.4%) who underwent eOBCS. Six mastectomy patients (60%) had reconstruction and 6 (60%) underwent external beam radiation therapy (EBRT). Reconstructions were completed in a staged fashion, and the mean cost of the index operation (mastectomy and tissue expander) was $17,816. These patients had one to three subsequent surgeries to complete their reconstruction, at a mean cost of $45,904. The mean cost of EBRT was $5542. Thirty-four eOBCS patients (44.7%) underwent 44 margin re-excisions, including 6 (7.9%) who underwent mastectomy. Sixty (78.9%) of the eOBCS patients had EBRT. The mean cost of their index operation was $6345; the mean cost of a re-excision was $3615; the mean cost of their mastectomies with reconstruction was $49,400; and the mean cost of EBRT was $6807. The cost of care for eOBCS patients remained lower than that for mastectomy patients, i.e. $17,318 versus $57,416. CONCLUSION: eOBCS is associated with a lower cost than mastectomy and had a low conversion rate to mastectomy.

Patient-Reported Outcomes 10 Years After Breast-Conserving Surgery for Early-Stage Breast Cancer.

BACKGROUND: Patient-reported outcomes (PROs) are a critical component of value-based care. Limited data exist describing long-term PROs in patients undergoing breast-conserving surgery (BCS). PATIENTS AND METHODS: Patients undergoing surgery for stage 0-III breast cancer at our institution from 2002 to 2012 who agreed to be contacted were invited to participate in a cross-sectional PRO study. Health-related quality of life outcomes using BREAST-Q, EORTC QLQ-C30, and EORTC QLQ-BR45 were collected. Patients reporting chemotherapy within 6 months of receiving the survey were excluded. For this work, we focused on patients who underwent BCS. Multivariable linear regression was performed to identify factors associated with PRO scores, adjusting for age, time since surgery, anatomic stage, molecular subtype, receipt of systemic and/or radiation therapy (RT), locoregional recurrence, or contralateral breast cancer. RESULTS: Among 562 interested and eligible patients, 437 (78%) responded; median time from surgery to survey completion was 10.4 years (interquartile range: 8.0-13.5). Median age at surgery was 53 years (standard deviation 9.8 years), ≥ 90% were white, had upfront surgery for early-stage disease, and completed adjuvant RT. Physical and psychological well-being scores were generally high, with more variation seen for sexual well-being and satisfaction with breasts. CONCLUSION: This study provides long-term PRO data for patients treated with BCS, demonstrating the ongoing association of breast cancer surgery with quality of life in the survivorship period and highlighting the importance of examining PROs beyond the perioperative period. These data also provide important reference values for the interpretation of PROs among women treated with BCS as we move towards value-based care.

Contemporary Analysis of Reexcision and Conversion to Mastectomy Rates and Associated Healthcare Costs for Women Undergoing Breast-Conserving Surgery.

PURPOSE: This study was designed to provide a comprehensive and up-to-date understanding of population-level reoperation rates and incremental healthcare costs associated with reoperation for patients who underwent breast-conserving surgery (BCS). METHODS: This is a retrospective cohort study using Merative™ MarketScan® commercial insurance data and Medicare 5% fee-for-service claims data. The study included females aged 18-64 years in the commercial cohort and females aged 18 years and older in the Medicare cohort, who underwent initial BCS for breast cancer in 2017-2019. Reoperation rates within a year of the initial BCS and overall 1-year healthcare costs stratified by reoperation status were measured. RESULTS: The commercial cohort included 17,129 women with a median age of 55 (interquartile range [IQR] 49-59) years, and the Medicare cohort included 6977 women with a median age of 73 (IQR 69-78) years. Overall reoperation rates were 21.1% (95% confidence interval [CI] 20.5-21.8%) for the commercial cohort and 14.9% (95% CI 14.1-15.7%) for the Medicare cohort. In both cohorts, reoperation rates decreased as age increased, and conversion to mastectomy was more prevalent among younger women in the commercial cohort. The mean healthcare costs during 1 year of follow-up from the initial BCS were $95,165 for the commercial cohort and $36,313 for the Medicare cohort. Reoperations were associated with 24% higher costs in both the commercial and Medicare cohorts, which translated into $21,607 and $8559 incremental costs, respectively. CONCLUSIONS: The rates of reoperation after BCS have remained high and have contributed to increased healthcare costs. Continuing efforts to reduce reoperation need more attention.

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

BACKGROUND: Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. METHODS: We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. RESULTS: The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). CONCLUSIONS: In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Immigration Status and Breast Cancer Surgery Quality of Care Metrics: A Population-Level Analysis.

INTRODUCTION: As immigrant women face challenges accessing health care, we hypothesized that immigration status would be associated with fewer women with breast cancer receiving surgery for curable disease, fewer undergoing breast conserving surgery (BCS), and longer wait time to surgery. METHODS: A population-level retrospective cohort study, including women aged 18-70 years with Stage I-III breast cancer diagnosed between 2010 and 2016 in Ontario was conducted. Multivariable analysis was performed to assess odds of undergoing surgery, receiving BCS and wait time to surgery. RESULTS: A total of 31,755 patients were included [26,253 (82.7%) Canadian-born and 5502 (17.3%) immigrant women]. Immigrant women were younger (mean age 51.6 vs. 56.1 years) and less often presented with Stage I/II disease (87.4% vs. 89.8%) (both p < .001). On multivariable analysis, there was no difference between immigrant women and Canadian-born women in odds of undergoing surgery [Stage I OR 0.93 (95% CI 0.79-1.11), Stage II 1.04 (0.89-1.22), Stage III 1.22 (0.94-1.57)], receiving BCS [Stage I 0.93 (0.82-1.05), Stage II 0.96 (0.86-1.07), Stage III 1.00 (0.83-1.22)], or wait time [Stage I 0.45 (-0.61-1.50), Stage II 0.33 (-0.86-1.52), Stage III 3.03 (-0.05-6.12)]. In exploratory analysis, new immigrants did not have surgery more than established immigrants (12.9% vs. 10.1%), and refugee women had longer wait time compared with economic-class immigrants (39.5 vs. 35.3 days). CONCLUSIONS: We observed differences in measures of socioeconomic disadvantage and disease characteristics between immigrant and Canadian-born women with breast cancer. Upon adjusting for these factors, no differences emerged in rate of surgery, rate of BCS, and time to surgery. The lack of disparity suggests barriers to accessing basic components of breast cancer care may be mitigated by the universal healthcare system in Canada.

A Prospective Study of Sentinel Node Biopsy Omission in Women Age ≥ 65 Years with ER+ Breast Cancer.

BACKGROUND: National guidelines recommend omitting SNB in older patients with favorable invasive breast cancer. However, there is a lack of prospective data specifically addressing this issue. This study evaluates recurrence and survival in estrogen receptor-positive/Her2- (ER+) breast cancer patients, aged ≥ 65 years who have breast-conserving surgery (BCS) without SNB. METHODS: This is a prospective, observational study at a single institution where 125 patients aged ≥ 65 years with clinical T1-2N0 ER+ invasive breast cancer undergoing BCS were enrolled. Patients were treated with BCS without SNB. Primary outcome measure was axillary recurrence. Secondary outcome measures include recurrence-free survival (RFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: From January 2016 to July 2022, 125 patients were enrolled with median follow-up of 36.7 months [95% confidence interval (CI) 35.0-38.0]. Median age was 77.0 years (range 65-93). Median tumor size was 1 cm (range 0.1-5.0). Most tumors were ductal (95/124, 77.0%), intermediate grade (60/116, 51.7%), and PR-positive (117/123, 91.7%). Radiation therapy was performed in 37 of 125 (29.6%). Only 60 of 125 (48.0%) who were recommended hormonal therapy were compliant at 2 years. Chemotherapy was administered to six of 125 (4.8%) patients. There were two of 125 (1.6%) axillary recurrences. Estimated 3-years rates of regional RFS, DFS, and OS were 98.2%, 91.2%, and 94.8%, respectively. Univariate Cox regression identified hormonal therapy noncompliance to be significantly associated with recurrence (p = 0.02). CONCLUSIONS: Axillary recurrence rates were extremely low in this cohort. These results provide prospective data to support omission of SNB in this patient population TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02564848.

Quantitative Biomarkers, Genomic Assays, and Demographics Associated with Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER-Negative Breast Cancer.

BACKGROUND: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups. METHODS: We analyzed the 2010-2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS." Logistic regression was performed. Adjusted odds ratios (AOR) were per 10-unit increase in ER%/PR%/Ki-67%. RESULTS: Overall, 42.3% underwent BCS after NACT, whereas 64.0% did after NET. Increasing ER% (AOR = 0.96, 95% confidence interval [CI] 0.94-0.97) or PR% (AOR=0.98, 95% CI 0.96-0.99) was associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS (AOR = 1.07, 95% CI 1.04-1.10). Breast-conserving surgery rates increased by ~20 percentage points, with Ki-67% ≥15 or RS >20. Patients with a low (43.0%, AOR = 0.50, 95% CI 0.29-0.88) or intermediate (46.4%, AOR = 0.58, 95% CI 0.41-0.81) RS were less likely than patients with a high RS (65.0%) to undergo BCS after NACT. Increasing ER% was associated with higher odds of BCS after NET (AOR = 1.09, 95% CI 1.01-1.17). Breast-conserving surgery rates increased by ~20 percentage points between ER <50% and >80%. In both cohorts, the odds of BCS were similar between 70-gene low-risk and high-risk groups. Asian or uninsured patients had lower odds of BCS. CONCLUSIONS: Neoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS.