Ipsilateral Breast Tumor Recurrence Research Articles

Patient Preference for Surgical Methods for Ipsilateral Breast Tumor Recurrence.

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. 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. 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. 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.

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

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). 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 73.4months. 1:3 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize selection bias. 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 inregional recurrence, distant metastasis, oroverall 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 3cm of the nipple, the CL group showed a significantly higher IBTR than the cBCS group before and after PSM. CL was associated with a higher rate ofIBTR 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.

Oncological outcomes of post neo adjuvant chemotherapy breast conservation surgery in patients with locally advanced breast cancer

Abstract Introduction: Breast cancer in India is phenotypically different with locally advanced breast cancers (LABCs) forming 30–50% of all cases. Use of neoadjuvant chemotherapy (NACT), among other things has contributed to surgeons using breast conservation surgery (BCS) in very selected patients with good results. Herein, we describe the oncological outcomes of BCS in LABC patients undergoing surgery post NACT. Patients and Methods: This is an ambispective observational cohort study conducted between January 1996 and December 2019 after approval by Institute Ethics Committee, to study the ipsilateral breast tumor recurrence (IBTR) in patients with LABC undergoing BCS post NACT. The secondary objectives were to ascertain the disease-free survival (DFS) and overall survival (OS) and factors associated with IBTR in these patients. Patients were staged according to the anatomic American Joint Committee on Cancer (AJCC) VIII Tumor Node Metastasis (TNM) classification and clinic-demographic, pathologic, treatment, and follow-up details were noted. Results: Out of 822 patients with LABC, 71 patients undergoing BCS post NACT were included. Average tumor size at presentation was 6.43 cm. The most common T stage was T3 (57.7%) and N stage was N1 (53.5%). The most common stage group was IIIB in 40.8%. Around 75% received anthracycline-based NACT with 28.2% having a complete clinical response. A pathological complete response was seen in 16 patients (22.5%). The mean follow-up duration was 6.14 years. A total of 25 patients had recurrences: five patients had IBTR (7%) and four had a local with regional recurrence. Two, 5, and 10 years OS were 94.0, 83.8, and 61.9%, respectively, and DFS were 87.8, 67.1, and 50.6%, respectively. A higher clinical T stage was associated with poor DFS (p = 0.01). The risk of IBTR was not found to significantly correlate with any of the standard prognostic factors. Conclusion: BCS post NACT in suitably selected patients of LABC is a safe and viable option without adversely affecting oncological outcomes.

Post-mastectomy reirradiation for ipsilateral T3N0M0 breast tumor relapse: apopulation-based study.

Post-mastectomy radiotherapy is commonly recommended for T3N0M0 breast cancer, particularly in the presence of adverse prognostic factors. However, for T3N0M0 ipsilateral recurrences following breast-conserving surgery and adjuvant radiotherapy, the situation is distinct. Recurrence alone signifies anegative prognostic factor. Moreover, tumor relapses within previously irradiated areas exhibit enhanced radioresistance, and reirradiation of the chest wall carries an escalated risk of radiation-induced toxicity. This study aimed to assess the impact of post-mastectomy reirradiation (PM-reRT) on patient outcomes in cases of ipsilateral T3N0M0 breast tumor recurrence, using data from the SEER database. We identified all patients who underwent treatment for primary non-metastatic breast cancer with breast-conserving surgery followed by adjuvant radiotherapy in the SEER database; among them, those who later experienced alocalized T3N0M0 breast tumor recurrence and underwent total mastectomy were included. The study's goal was to compare overall survival (OS) and cancer-specific survival (CSS) between patients who underwent only mastectomy versus those who had mastectomy followed by adjuvant PM-reRT for their ipsilateral T3N0M0 breast tumor relapse. From 2000 to 2020, the SEER database recorded 44patients with an ipsilateral T3N0M0 breast tumor recurrence after initial conservative treatment, managed with total mastectomy. No statistically significant differences in OS or CSS were observed between patients undergoing mastectomy (MT) alone versus those receiving MT combined with PM-reRT (p = 0.68 and p = 0.86, respectively). Five-year OS rates for the MT and MT + PM-reRT cohorts were 49.5% [95% CI: 29.9-81.8] and 41.7% [10.0-100.0], respectively, while 5‑year CSS rates were 51.6% [12.0-99.5] and 58.3% [15.2-100.0], respectively. For patients undergoing total mastectomy after an ipsilateral T3N0M0 breast tumor recurrence, subsequent to initial breast cancer treatment involving breast-conserving surgery and adjuvant radiotherapy, chest wall reirradiation does not enhance survival outcomes. As such, it should not be routinely performed.

Hypofractionated Partial Breast Irradiation With Intensity-Modulated Radiotherapy in Early Breast Cancer or Carcinoma In Situ: An Investigational Short-Term Analysis.

This study aimed to analyze the treatment outcomes and adverse effects of moderately hypofractionated partial breast irradiation (PBI) in patients with early breast cancer. In total, 473 patients with early breast cancer or carcinoma in situ were diagnosed with Tis or T1N0 disease and underwent PBI following breast-conserving surgery. All histologic tumor types, close surgical margins within 1 mm of the tumor, and multifocal tumors were included in this study. A radiation dose of 50 Gy in 20 fractions was delivered over 4 weeks using intensity-modulated radiotherapy technique. Dosimetric data, recurrence patterns, survival outcomes, and adverse events were retrospectively analyzed. During a median follow-up of 28.9 months, seven patients (1.5%) experienced ipsilateral breast tumor recurrence (IBTR). Two patients had regional recurrence, four patients developed contralateral breast cancer, and no distant metastases were observed. The locoregional recurrence rate in the ipsilateral breast was 1.8%. Two deaths occurred during the follow-up period, but were not attributed to breast cancer. The 2-year disease-free survival and 2-year overall survival rates were was 94.0% and 99.8%, respectively. Acute adverse events occurred in 131 patients (27.1%), and were distributed among all grades, with only two patients (0.4%) experiencing grade 3 events. Late adverse events were noted in 16 patients (3.4%), and were distributed among all grades, including grade 3 events in four patients (0.8%). No grade 4 or 5 events were observed. Hypofractionated PBI demonstrated favorable IBTR rates in patients with early breast cancer, with low incidence of acute and late toxicities in the short-term analysis.

The practice patterns and perceptions of surgeons in Singapore regarding breast-conserving surgery

Breast-conserving surgery (BCS) is often the preferred treatment in operable breast cancer.1 While tumour biology and systemic therapy are major determinants of disease control, surgical effectiveness remains a key factor in ipsilateral breast tumour recurrence.1 As heterogeneity in surgical approach has been observed, we sought to understand Singaporean surgeons’ practice patterns and perceptions. Breast surgeons from Singapore’s public and private healthcare institutions were invited to participate in a Dillman’s Tailored Design Method online-based survey and their responses are summarised in Table 1. We discuss how surgeons’ perception may influence overall management.

The Feasibility of Omitting Postoperative Radiotherapy in Japanese Patients With Ductal Carcinoma In Situ of Breast Treated With Breast-Conserving Surgery.

Background To analyze the feasibility of omitting postoperative radiotherapy (PORT) after breast-conserving surgery (BCS) in Japanese patients with ductal carcinoma in situ (DCIS). Materials and methods We retrospectively analyzed 88 patients with small pure DCIS (median diameter 1.1 cm, ≤ 4 cm) who underwent BCS with (n = 39) or without (n = 49) PORT.The primary and secondary endpoints were ipsilateral breast tumor recurrence (IBTR) and overall survival (OS), respectively, between the groups that received PORT and those that did not. Results The PORT group included a high number of margin-positive cases. The incidence of IBTR was 2.4% (95% confidence interval (CI), 0.3-15.7%) and 2.8% (95% CI, 0.4-18.2%) at five years and 5.5% (95% CI, 1.4-20.6%) and 2.8% (95% CI, 0.4-18.2%) at 10 years in patients without and with PORT, respectively (p = 0.686). In the margin-negative group, only one patient showed IBTR without RT (2.3%), whereas no patient with PORT experienced IBTR (0%). To date, there have been no regional or distant metastases; therefore, no patient has experienced breast cancer-related deaths.The OS rates were 97.7% (95% CI, 84.9-99.6%) and 100% at 10 years in patients without and with PORT, respectively (p = 0.372). Conclusion This study suggests that the omission of PORT after BCS could be a feasible option for selected Japanese patientsbut requires further investigation to identify the low-risk factor in patients who can omit PORT.

Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection

Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death. To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer. This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023. Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not. The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality. Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality. The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.

Adjuvant Breast Radiation Therapy for Early-Stage Breast Cancer or Ductal Carcinoma In-Situ in the Breast: A Systematic Review and Network Meta-Analysis of Randomized Trials

For selected patients with early-stage breast cancer (BC) or ductal carcinoma in-situ (DCIS) in the breast, adjuvant breast radiation therapy (RT) approaches include partial breast irradiation (PBI), altered fractionation (AF) whole breast irradiation (WBI) or tumor bed boost (TBB). However, it is unclear which is the optimal approach. This study aims to compare the effects of different PBI, AF-WBI and TBB options on ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and patient reported cosmesis (PRC) outcomes. We searched various biomedical electronic databases for eligible randomized trials (RCTs) from date of inception to January 2023. We constructed six separate random effects frequentist network meta-analyses (NMA) to compare the effects of various PBI options using WBI as the reference; various AF-WBI options using conventional fractionated (CF) WBI as the reference and various TBB options using no TBB as the reference on IBTR and OS. The GRADE approach was used to assess the certainty of evidence. The synthesis without meta-analysis approach was pre-specified for evaluation of PRC in anticipation of various assessment and reporting methods. We included 34 RCTs comprising 49,899 participants and 11 treatment options. Evidence suggests that accelerated PBI (Hazard Ratio (HR) 1.36 (95% confidence interval (CI) 0.77 - 2.41, moderate certainty), moderately hypofractionated (MHF) PBI (HR 1.38 (0.60 - 3.19), moderate certainty) and intraoperative PBI (HR 1.47 (0.81 - 2.68), low certainty) was associated with a modest but not statistically significant increase in the hazards for IBTR when compared to WBI. There was moderate certainty evidence that there were no significant differences among the accelerated ultra-hypo fractionated (AUHF) WBI (HR 0.76 (0.50 - 1.14)), MHF-WBI (HR 0.99 (0.84 - 1.16)) or UHF-WBI (HR (1.35 (0.47 - 3.92)) when compared with CF-WBI for IBTR. The effects of sequential TBB (seqTBB) (HR 0.61 (0.52 - 0.70), high certainty) and simultaneous integrated TBB (simTBB) (HR 0.77 (0.55 - 1.09), moderate certainty) on IBTR were similar when compared to no TBB. There were no significant differences in OS between PBI options and WBI, AF-WBI options and CF-WBI, TBB options and no TBB. Among the PBI vs WBI trials, MHF-PBI and APBI may be associated with fewer adverse PRC events. Among the AF-WBI vs CF-WBI trials, half of the included trials reported fewer adverse PRC events with MHF-WBI. SeqTBB and simTBB had similar adverse PRC outcome. There were no significant differences among the PBI, AF-WBI and TBB options for IBTR and OS. PBI and AF-WBI may be associated with less adverse PRC events compared with WBI and CF-WBI respectively. There was no evidence to suggest a difference between seqTBB and simTBB for PRC outcome. This study is registered with PROSPERO CRD 42021245074.

Reappraisal of an Adequate Negative Margin Following Breast Conservation Therapy in Young Patients with Invasive Breast Cancer

This study aimed to examine the relationship between resection margin (RM) width and ipsilateral breast tumor recurrence (IBTR). The current definition of an adequate negative margin was validated in young breast cancer patients (<40 years). This study included 4,042 patients who underwent breast conservation therapy between 2006 and 2012. There were 595 women <40 years (14.7%). Re-excision to achieve a wider RM was not considered in patients with no ink on tumor. Systemic treatments were administered in 3,985 patients (98.6%). The impact of RM width on the incidence of IBTR was assessed using narrowly specified intervals (positive, >0 to <1 mm, 1 to <2 mm, 2 to <3 mm, and ≥3 mm). A significant relationship was observed between RM width and incidence of IBTR. In young women, the 10-year cumulative incidence rates of IBTR were 21.6% for positive RM, 13.9% for >0 to <1 mm, 10.9% for 1 to <2 mm, 5.7% for 2 to <3 mm, and 5.8% for ≥3 mm (p <0.01). The corresponding incidence rates of IBTR in women ≥40 years were 8.6%, 8.0%, 4.4%, 2.7%, and 2.1%, respectively (p <0.01). The difference in the incidence of IBTR between each RM width interval increased over time, and the magnitude of the increment was greater in young women. RM width was the only risk factor for IBTR in young women. The relationship between RM width and IBTR was definite in young women. Compared with women ≥40 years, young women might have long-term benefits from a wider RM than no ink on tumor.

Intra-Operative Radiotherapy (IORT) in Breast Conserving Therapy in Early-Stage Breast Cancer and DCIS

Initial breast intra-operative radiotherapy (IORT) results in clinical trials were encouraging though with longer follow up, increased local recurrences have been reported compared with whole breast radiation or other partial breast radiation including accelerated partial breast irradiation (APBI) methods. The goal of the study is to report our prospective single institution IORT breast study outcomes of local recurrence (LR) including true recurrence and breast elsewhere failures, breast cancer specific survival (BCSS), and overall survival (OS) with low energy x-ray IORT in early-stage breast cancer or ductal carcinoma in situ. A total of 480 patients with early-stage breast cancer or DCIS were prospectively enrolled in an IRB approved single institution trial and treated with low energy X-ray IORT 20 Gy at time of breast-conserving surgery. Eligibility criteria included ≥ 45 years of age with unifocal tumors < 3 cm deemed candidates for partial mastectomy. Supplemental external beam radiation was recommended for patients with high-risk surgical pathology including multifocal disease, positive nodes, close margins < 2 mm, or lymphovascular invasion. Ipsilateral breast tumor recurrences were classified as true recurrence versus elsewhere failure by location and histology: same/different quadrant and similar/different histology. Kaplan-Meier methods were used to estimate survival probabilities across time. Median age of enrolled patients was 64 years with the majority of patients having favorable phenotype with 94% ER+ and 93% Her-2 - disease. 110 patients (23%) had supplemental EBRT delivered; 103 to the whole breast and 7 to the breast and regional nodes. At a median follow up of 73 months (range 17 - 131 months), there were 23 (4.8%) ipsilateral breast tumor recurrences, of which 9 were true recurrences (1.9%) and 14 elsewhere failures (2.9%). One patient with true recurrence and 3 patients with elsewhere breast failures synchronously presented with clinical or radiographic regional node involvement. Seven patient developed contralateral breast cancer and 8 patients developed distant metastases during the follow-up period. There were 2 breast cancer related deaths. At 6-years, overall survival rate was 96.8% and breast cancer specific survival was 98.7%. Our study outcomes reflect similar outcomes as other reported IORT studies with electron or low energy X-ray in breast cancer, with higher risk of local failure than historical whole breast and other partial breast radiation techniques. This supports current radiation society guidelines for IORT monotherapy for breast cancer to be optimally considered in the context of prospective clinical trials.

Radiotherapy versus low-dose tamoxifen following breast-conserving surgery for low-risk and estrogen receptor-positive breast ductal carcinoma in situ: an international open-label randomized non-inferiority trial (TBCC-ARO DCIS Trial)

BackgroundRadiotherapy (RT) following breast-conserving surgery (BCS) is mainly used to decrease the rate of ipsilateral breast tumor recurrence (IBTR) in women with breast ductal carcinoma in situ (DCIS). Recent studies have demonstrated that low-dose tamoxifen significantly reduces IBTR in breast DCIS. Here, we aim to determine whether the administration of low-dose tamoxifen is non-inferior to RT in preventing IBTR in patients with low-risk characteristics of breast DCIS.Methods/designThis is a prospective, international, open-label, randomized, non-inferiority trial. Patients with low-risk clinicopathologic features (> 40 years old, low risk of breast cancer susceptibility gene (BRCA) 1 and BRCA2 mutations, mammographically detected unicentric and non-mass lesions, low- or intermediate-grade without comedo or necrosis, measuring < 2.5 cm with margins ≥ 3 mm, and estrogen receptor-positive status) of DCIS who underwent BCS will be randomized at a 1:1 ratio to either receive tamoxifen (5 mg/day) for 5 years or undergo RT with conventional fractions (50 Gy in 25 fractions) or hypofractionations (40.05 Gy in 15 fractions). Randomization will be stratified by the Taiwan Breast Cancer Consortium. As approximately 5% of patients cannot tolerate the side effects of low-dose tamoxifen and will receive RT, we estimate that 405 patients will be randomized to a low-dose tamoxifen arm and 405 patients to the RT arm, according to a non-inferiority margin within 5% of IBTR difference and 90% β-power noticing non-inferiority. The primary endpoints are breast tumor recurrence, including ipsilateral, regional, contralateral, and distant recurrence of breast DCIS or invasive cancer. The secondary endpoints are overall survival and adverse effects of RT and tamoxifen. Translational studies will also be conducted for this trial.DiscussionThis is the first non-inferiority trial on breast DCIS. This study will provide an important recommendation for clinical physicians on whether to use low-dose adjuvant tamoxifen for patients with low-risk breast DCIS who do not want to receive adjuvant RT.Trial registrationClinicalTrials.gov, ID: NCT04046159, Registered on April 30, 2019.

Pattern of practice of re-irradiation for ipsilateral breast tumor recurrence in Italy: a survey by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

The Re-irradiation and the Breast Cancer Working Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey to provide an overview of the policies for breast cancer (BC) re-irradiation (re-RT) among the Italian radiotherapy (RT) centers. In October 2021, 183 RT centers were invited to answer a survey: after an initial section about general aspects, the questionnaire focused on radiation oncologists' (ROs) attitude toward re-RT in three different scenarios: ipsilateral breast tumor recurrence (IBTR) treated with second conservative surgery, IBTR treated with mastectomy and inoperable IBTR. Surveyed ROs were also asked to express their interest in being involved in a prospective trials. Seventy-seven/183 (42.0%) centers answered the Survey, only one RO per center was requested to answer. In particular, 86.5% ROs declared to have performed "curative" re-RT for IBTR during the previous two years (2019-2020): 76.7% respondents administered re-RT after second BCS, 50.9% after mastectomy, and 48.1% for inoperable IBTR. Re-RT practice varied widely among centers in terms of treatment volumes, dose and fractionation schedules, techniques and dose-volume constraints for organs at risks (OARs). Forty-six participants (59.7%) expressed their interest in participating in a prospective study investigating BC re-RT. About one out of three RT centers in Italy delivered re-RT for IBTR. Nevertheless, practice of re-RT varied widely among centers highlighting the needs for prospective studies to improve knowledge in this field.

Does Non-Classic Lobular Carcinoma In Situ at the Lumpectomy Margin Increase Local Recurrence?

The clinical significance of nonclassic, lobular carcinoma in situ (NC-LCIS) at the surgical margin of excisions for invasive cancer is unknown. We sought to determine whether NC-LCIS at or near the margin in the setting of a concurrent invasive carcinoma is associated with risk of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR). Patients with stage 0-III breast cancer and NC-LCIS who underwent lumpectomy between January 2010 and January 2022 at a single institution were retrospectively identified. NC-LCIS margins were stratified as <2 mm, ≥2 mm, or within shave margin. Rates of IBTR and LRR were examined. A total of 511 female patients (median age 60 years [interquartile range (IQR) 52-69]) with NC-LCIS and an associated ipsilateral breast cancer with a median follow-up of 3.4 years (IQR 2.0-5.9) were identified. Final margins for NC-LCIS were ≥2 mm in 348 patients (68%), <2 mm in 37 (7.2%), and within shave margin in 126 (24.6%). Crude incidence of IBTR was 3.3% (n = 17) and that of LRR was 4.9% (n = 25). There was no difference in the crude rate of IBTR by NC-LCIS margin status (IBTR rate: 3.7% ≥2 mm, 0% <2 mm, 3.2% within shave margin, p = 0.8) nor in LRR (LRR rate: 4.9% ≥2 mm, 2.7% <2 mm, 5.6% within shave margin, p = 0.9). For completely excised invasive breast cancers associated with NC-LCIS, extent of margin width for NC-LCIS was not associated with a difference in IBTR or LRR. These data suggest that the decision to perform reexcision of margin after lumpectomy should be driven by the invasive cancer, rather than the NC-LCIS margin.

Association of Sarcopenia With Toxicity-Related Discontinuation of Adjuvant Endocrine Therapy in Women With Early-Stage Hormone Receptor–Positive Breast Cancer

Sarcopenia, an age-related decline in muscle mass and physical function, is associated with increased toxicity and worse outcomes in women with breast cancer (BC). Sarcopenia may contribute to toxicity-related early discontinuation of adjuvant endocrine therapy (aET) in women with hormone receptor-positive (HR+) BC but remains poorly characterized. This multicenter, retrospective cohort study included consecutive women with stage 0-II HR+ BC who received breast conserving therapy (lumpectomy and radiation therapy) and aET from 2011 to 2017 with a 5-year follow-up. Skeletal muscle index (SMI, cm2/m2) was analyzed using a deep learning model on routine cross-sectional radiation simulation imaging; sarcopenia was dichotomized according to previously validated reports. The primary endpoint was toxicity-related aET discontinuation; logistic regression analysis evaluated associations between SMI/sarcopenia and aET discontinuation. Cox regression analysis evaluated associations with time to aET toxicity, ipsilateral breast tumor recurrence (IBTR), and disease-free survival (DFS). A total of 305 women (median follow-up, 89 months) were included with a median age of 67 years and early-stage BC (12% stage 0, 65% stage I). A total of 60 (20%) women experienced toxicity-related aET discontinuation. Sarcopenia was associated with toxicity-related early discontinuation of aET (odds ratio, 2.18; P=.036) and shorter time to aET toxicity (hazard ratio [HR], 1.62; P=.031). SMI or sarcopenia were not independently associated with IBTR or DFS; toxicity-related aET discontinuation was associated with worse IBTR (HR, 9.47; P=.002) and worse DFS (HR, 4.53; P=.001). Among women with early-stage HR+ BC who receive adjuvant radiation therapy and hormone therapy, sarcopenia is associated with toxicity-related early discontinuation of aET. Further studies should validate these findings in women who did not receive adjuvant radiation therapy. These high-risk patients may be candidates for aggressive symptom management and/or alternative treatment strategies to improve outcomes.

Long-term outcomes of intraoperatively-placed applicator brachytherapy for rapid completion of breast conserving treatment: An analysis of a prospective registry data.

To evaluate the long-term outcome of accelerated partial breast irradiation utilizing intraoperatively placed applicator-based brachytherapy (ABB) in early-stage breast cancer. From our prospective registry, 223 patients with pTis-T2, pN0/pN1mic breast cancer were treated with ABB. The median treatment duration including surgery and ABB was 7days. The prescribed doses were 32Gy/8 fx BID (n=25), 34Gy/10 fx BID (n=99), and 21Gy/3 fx QD (n=99). Endocrine therapy (ET) adherence was defined as completion of planned ET or≥80% of the follow-up (FU) period. Cumulative incidence of ipsilateral breast tumor recurrence (IBTR) was estimated and influencing factors for IBTR-free survival rate (IBTRFS) were analyzed. 218/223 patients had hormone receptor-positive tumors, including 38 (17.0%) with Tis and 185 (83.0%) with invasive cancer. After a median FU of 63months, 19 (8.5%) patients had recurrence [17 (7.6%) with an IBTR]. Rates of 5-year IBTRFS and DFS were 92.2% and 91.1%, respectively. The 5-year IBTRFS rates were significantly higher for post-menopausal women (93.6% vs. 66.4%, p=0.04), BMI<30kg/m2 (97.4% vs. 88.1%, p=0.02), and ET-adherence (97.5% vs. 88.6%, p=0.02). IBTRFS did not differ with dose regimens. Postmenopausal status, BMI<30kg/m2, and ET- adherence predicted favorable IBTRFS. Our results highlight the importance of careful patient selection for ABB and encouragement of ET compliance.

Locoregional Recurrence Patterns in Patients With Different Molecular Subtypes of Breast Cancer

While numerous studies have consistently reported that the molecular subtypes of breast cancer (BC) are associated with different patterns of distant metastasis, few studies have investigated the association of tumor subtypes with locoregional recurrence. To investigate the patterns of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), and contralateral BC (CBC) according to tumor subtypes. This retrospective cohort study used the clinical records of patients who underwent BC surgery at a single institution in South Korea between January 2000 and December 2018. Data were analyzed from May 1, 2019, to February 20, 2023. Ipsilateral breast tumor recurrence, RR, and CBC events. The primary outcome was differences in annual incidence patterns of IBTR, RR, and CBC according to tumor subtypes. Hormone receptor (HR) status was assessed by immunohistochemical staining assay, and ERBB2 status was evaluated according to American Society of Clinical Oncology and College of American Pathologists guidelines. A total of 16 462 female patients were included in the analysis (median age at time of operation, 49.0 years [IQR, 43.0-57.0 years]). The 10-year IBTR-, RR-, and CBC-free survival rates were 95.9%, 96.1%, and 96.5%, respectively. On univariate analysis, HR-/ERBB2+ tumors had the worst IBTR-free survival (vs HR+/ERBB2- subtype: adjusted hazard ratio, 2.95; 95% CI, 2.15-4.06), while the HR-/ERBB2- subtype had the worst RR- and CBC-free survival among all subtypes (vs HR+/ERBB2- subtype, RR: adjusted hazard ratio, 2.95; 95% CI, 2.37-3.67; CBC: adjusted hazard ratio, 2.12; 95% CI, 1.64-2.75). Subtype remained significantly associated with recurrence events in Cox proportional hazards regression analysis. Regarding the annual recurrence pattern, the IBTR patterns of HR-/ERBB2+ and HR-/ERBB2- subtypes showed double peaks, while HR+/ERBB2- tumors showed a steadily increasing pattern without distinguishable peaks. Additionally, the HR+/ERBB2- subtype seemed to have a steady RR pattern, but other subtypes showed the highest RR incidence at 1 year following surgery, which then gradually decreased. The annual recurrence incidence of CBC gradually increased among all subtypes, and patients with the HR-/ERBB2- subtype had a higher incidence than patients with other subtypes over 10 years. Younger patients (age ≤40 years) had greater differences in IBTR, RR, and CBC patterns between subtypes than did older patients. In this study, locoregional recurrence occurred with different patterns according to BC subtypes, with younger patients having greater differences in patterns among subtypes than older patients. The findings suggest that tailoring surveillance should be recommended regarding differences in locoregional recurrence patterns according to tumor subtypes, particularly for younger patients.

Impact of Atypical Hyperplasia at Surgical Margins on breast cancer outcomes in patients treated with neoadjuvant chemotherapy.

Women with atypical hyperplasia (AH) is associated with a higher risk of future breast cancer. However, whether AH found at margins in patients with breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) needs re-excision is not well-defined. The aim of the present study was to evaluate the impact of AH at the surgical margins on the local recurrence and survival outcomes in breast cancer patients treated with NAC and BCS. A retrospective analysis comparing patients who treated with NAC and BCS with AH at the margins to those without AH was performed. 598 patients were included in this study. The 5-year rates of ipsilateral breast tumor recurrence (IBTR) were 4.6% and 6.2% in patients with and without AH, respectively. No significant differences were observed among the two groups in terms of IBTR, DMFS, or OS. HER2 overexpressing breast cancer patients with severe AH at margins have a significantly higher risk of IBTR compared to those without severe AH. Our study suggests that the presence of AH at the surgical margins of BCS in patients who received NAC does not appear to increase the risk of ipsilateral breast cancer. Therefore, there is no need for surgeons to routinely perform additional re-excision of AH found at the margins of BCS in these patients. However, selective re-excision should be considered in certain cases, particularly in patients with HER2 overexpression.

Can breast cancer be reirradiated?

Salvage mastectomy is still the standard procedure for ipsilateral breast tumor recurrence. A second breast-conserving approach with re-irradiation is considered nowadays feasible in selected patients, with good results in terms of local control and tolerance. In this work we summarize the different radiation techniques and their results in order to define recommendations to help groups starting to consider this approach in their institutions. Although the difficulty due to the low rate of breast cancer recurrences after first breast conserving therapy, further clinical trials are needed to confirm these results.

Combining histological grade, TILs, and the PD-1/PD-L1 pathway to identify immunogenic tumors and de-escalate radiotherapy in early breast cancer: a secondary analysis of a randomized clinical trial

BackgroundThe implementation of immunological biomarkers for radiotherapy (RT) individualization in breast cancer requires consideration of tumor-intrinsic factors. This study aimed to investigate whether the integration of histological grade, tumor-infiltrating lymphocytes...