Ipsilateral Breast Tumor Recurrence Rates Research Articles

Abstract PO1-01-07: Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. A retrospective study

Abstract OBJECTIVE To evaluate the efficacy of combined treatment with ultrasound-guided cryoablation and endocrine therapy (ET) in hormone receptor-positive (ER+), HER2-negative (HER-) invasive breast cancer (BC) patients with clinical stage I/II who are not candidates for axillary surgery. PATIENTS AND METHODS Patients with ER+, HER- invasive BC in clinical stage I/II who did not undergo sentinel lymph node biopsy (SLNB) or target axillary dissection (TAD) were included. They received treatment consisting of ultrasound-guided cryoablation combined with daily letrozole 2.5 mg orally. Cryoablation was performed as the initial treatment for BC < 15mm, followed by adjuvant ET, while neoadjuvant ET was administered for 6-12 months before cryoablation for BC ≥ 15mm. Cryoablation was performed using the ICEfx Galil argon gas system (Boston Scientific, USA) and the ProSense liquid nitrogen system (IceCure Medical Ltd, Caesarea, Israel). Follow-up breast ultrasound examinations were conducted every six months. Patients with a minimum follow-up of 12 months after cryoablation were included in the study. Core needle biopsies were performed if recurrence was suspected, and rescue cryoablation was considered for confirmed relapse. The tolerance and safety of the procedures were recorded. RESULTS From March 2019 to July 2023, a total of 96 patients with 105 ER+, HER2- invasive BC in clinical stage I/II who did not undergo SLNB or TAD were treated with ultrasound-guided cryoablation and ET. Among them, 58 patients (aged 58-96 years, mean 83, SD ±7.64) with 64 BC lesions (ranging from 5 to 60mm, mean 17, SD ±13.75) were followed up for a minimum of 12 months, with a mean follow-up period of 24 months (ranging from 12 to 50 months). The invasive carcinomas included 40 ductal, 16 lobular, 5 colloid, and 3 papillary cases. The ipsilateral breast tumor recurrence rate was 1,72% (1/58 patients). One patient with lobular carcinoma experienced a relapse at 17 months. Rescue cryoablation was performed, and after 25 months, she remains free of recurrence. Therefore, local control was achieved in all patients. Six patients died from causes unrelated to BC during the follow-up period. All procedures were well-tolerated with local anesthesia, and no serious complications were reported. CONCLUSION Ultrasound-guided cryoablation with ET constitutes an effective combined treatment for the local control of ER+, HER2- BC in patients with clinical stage I/II and omission for surgical axillary staging. Cryoablation is a very well tolerated procedure without morbidity. Citation Format: José María Oliver Goldaracena, Pilar Zamora, Covadonga Marti, Vicenta Córdoba Chicote, Maria José Roca Navarro, Diego Garrido Alonso, Ylenia Navarro Monforte, Teresa Diaz de Bustamante Durban, Fernando García Martínez, Jose Ignacio Sanchez-Mendez, Elisa York Pineda, Laura Yebenes Gregorio, Adolfo Loayza, Laura Frías Aldeguer, Elisa Moreno Palacios, Marcos Melendez Gisper, Joaquin Gomez Ramirez, Luis Asensio Gómez, Virginia Martínez Marín, David Hardisson Hernáez, Alberto Berjón García. Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. A retrospective study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-07.

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.

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.

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.

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.

Impact of multifocal or multicentric disease on local recurrence and survival in breast cancer patients with or without BRCA1/2 variants

Multifocal or multicentric (MFMC) breast cancer is mainly focused on breast cancer patients with unknown BRCA status, the incidence and clinical relevance of MFMC disease in BRCA1/2 carriers is less explored to date. Our study was to investigate the incidence of MFMC disease in BRCA1/2 carriers and whether MFMC disease influences local recurrence and clinical outcomes. In this retrospective study, 479 breast cancer patients with BRCA1/2 variants and 1437 age-matched noncarriers were enrolled and patients received either breast-conserving therapy (BCT) or mastectomy with or without radiotherapy. The rates of MFMC disease in BRCA1 and BRCA2 carriers, and noncarriers were 33.0% (61 of 185), 37.4% (110 of 294), and 31.2% (449 of 1437), respectively. MFMC disease in BRCA2 carriers was significantly higher than that in noncarriers (P = 0.039). After a median follow-up of 8.1years, among patients treated with BCT, BRCA2 carriers with MFMC disease experienced a significantly higher rate of ipsilateral breast tumor recurrence (IBTR) than those with unifocal disease (16.7% vs 4.1%, P = 0.044). Moreover, BRCA2 carriers with MFMC disease had a significantly worse RFS (unadjusted hazard ratio [HR], 3.65 [95% CI 1.40-9.52]; P = 0.008), DRFS (unadjusted HR, 3.07 [95% CI 1.07-8.80]; P = 0.037), and OS (unadjusted HR, 4.96 [95% CI 1.18-20.02]; P = 0.029) than those with unifocal disease when treated with BCT. MFMC breast cancer is more common in BRCA2 carriers, and BRCA2 carriers with MFMC disease treated with BCT exhibit a higher rate of IBTR and may have a poor survival.

Intraoperative Radiation Therapy: A Large Integrated Health Care System's Approach and Outcomes.

Introduction Intraoperative radiation therapy (IORT) may not be as effective in the community compared with clinical trials. Methods The authors reviewed data from the electronic health records of patients who received IORT between February 2014 and February 2020 at a single center within a large integrated health care system. The primary outcome was ipsilateral breast tumor recurrence. Results Of 5731 potentially eligible patients, 245 (4.3%) underwent IORT (mean age: 65.4 ± 0.4 years; median follow-up time: 3.5 years ± 2.2 months). According to the American Society for Radiation Oncology's accelerated partial breast irradiation guidelines based on final pathology, 51% of patients were suitable candidates for IORT, 38.4% were cautionary, and 10.6% were unsuitable. For adjuvant therapy, 6.5% had consolidative whole breast irradiation, and 66.4% received endocrine treatment. At the median follow-up time of 3.5 years, overall ipsilateral breast tumor recurrence was 3.7%. Recurrences tended to be more frequent in patients who refused or did not complete endocrine treatment than in those who received it (7.4% vs 1.9%, p = 0.07). The complication rate was 14.7%, with seroma being the most common (8.2%). Discussion The IORT ipsilateral breast tumor recurrence rate of 3.7% confirms a higher-than-expected rate compared to randomized clinical trials, possibly due to less compliance with endocrine therapy. Conclusion The authors subsequently revised their IORT protocol to require endocrine treatment as a part of the IORT treatment plan and to strongly recommend adjuvant whole breast irradiation for all patients deemed cautionary or unsuitable for IORT according to the American Society for Radiation Oncology's accelerated partial breast irradiation guidelines.

Abstract P1-09-03: Impact of BRCA1/2 pathogenic variants on ipsilateral breast tumor recurrence and prognosis following breast-conserving surgery

Abstract Background The risk of ipsilateral breast tumor recurrence (IBTR) and the prognostic outcome of breast-conserving surgery (BCS) for germline BRCA1/2 pathogenic variant (BRCA1/2+) carriers remain controversial. We examined differences in IBTR and prognosis between BRCA1/2+ carriers and non-carriers following BCS for breast cancer. Methods Clinical and pathological data were collected by retrospectively reviewing charts of consecutive patients with stage 0-III breast cancer who underwent genetic testing for germline BRCA1/2 and BCS between 1996 and 2020. Patients with variants of breast cancer-associated genes other than BRCA1/2 were excluded. We compared the incidence of IBTR and prognosis, including overall survival (OS), breast cancer-specific survival (BCSS), and distant recurrence-free survival (DRFS), between BRCA1/2+ carriers and non-carriers. Results We analyzed 551 patients (587 breasts with cancer), including 30 BRCA1+ carriers (32 breasts) and 31 BRCA2+ carriers (32 breasts). The median follow-up was 5.8 years (7.2 and 5.3 years for carriers and non-carriers, respectively). The median age at breast cancer diagnosis was 43 and 46 years for carriers and non-carriers, respectively, indicating younger onset of cancer in carriers (age ≤ 40 years; 46.9% for carriers vs. 27.5% for non-carriers, p = 0.001). In carriers, breast cancer more frequently expressed estrogen receptor-negative (56.2% for BRCA1+ carriers and 15.6% for BRCA2+ carriers vs. 22.0% for non-carriers, p = 0.013), progesterone receptor-negative (62.5% for BRCA1+ carriers and 31.3% for BRCA2+ carriers vs. 29.5%, p = 0.005), nuclear grade III (45.3% for carriers vs. 29.5% for non-carriers, p = 0.010), or a higher Ki-67 index (Ki-67 index &amp;gt; 20) (89.5% vs. 61.8%, p = 0.001) than non-carriers. Moreover, carriers underwent chemotherapy more frequently than non-carriers (62.5% vs. 42.4%, p = 0.002). Cancer stage, tumor size, HER2 status, presence of lymphovascular invasion, and the rate of positive or close surgical margins did not statistically differ between the examined groups. No statistical differences were detected in the number of patients who underwent whole-breast radiotherapy following BCS: 59 breasts in carriers and 503 in non-carriers (92.2% vs. 96.4%). During follow-up, we noted that 9 breasts of BRCA1/2+ carriers (5 [15.6%] for BRCA1+ and 4 [12.5%] for BRCA2+) and 35 breasts (6.7%) of non-carriers developed IBTR (p = 0.035). In an analysis excluding patients who did not undergo radiotherapy, the rate of IBTR remained significantly higher in BRCA1/2+ carriers (p = 0.034) than that in non-carriers. The median time to IBTR was 10.2 years in carriers (10.2 years for BRCA1+ and 8.5 years for BRCA2+) and 3.5 years in non-carriers. Carriers were more likely than non-carriers to exhibit distinct subtypes of recurrent tumors in the ipsilateral breast (66.7% for carriers vs. 19.4% for non-carriers, p = 0.006), occurring in a different quadrant from the primary tumor (50.0% vs. 27.3%, p = 0.215). No significant differences in OS (p = 0.068), BCSS (p = 0.109), or DRFS (p = 0.359) were noted between carriers and non-carriers. Conclusion BRCA1/2+ carriers exhibited a higher risk of IBTR after BCS and a longer time to IBTR than non-carriers. One limitation of the present study is a longer follow-up period for carriers than for non-carriers, as carriers typically underwent long-term observation at our institution; hence, further data accumulation is warranted for validating these findings. Subtypes and quadrants of IBTR were frequently distinct in carriers, indicating the increased incidence of new primary breast cancer. Although the prognosis did not differ between carriers and non-carriers, our results suggest the necessity for long-term intensive breast surveillance of BRCA1/2+ carriers after BCS. Citation Format: Sakiko Kondo, Kumiko Kida, Misato Suzuki, Chika Fukano, Atsushi Yoshida, Naoki Hayashi, Junko Takei, Michiko Yamanaka, Hideko Yamauchi. Impact of BRCA1/2 pathogenic variants on ipsilateral breast tumor recurrence and prognosis following breast-conserving surgery [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-03.

Clinical significance of tumor cell seeding associated with needle biopsy in patients with breast cancer

Background/ObjectiveThe occurrence of iatrogenic tumor cell seeding (seeding) in needle tract scars formed by core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) is well known. Some risk factors for seeding have been reported, but the clinicopathological risk factors and its prognosis have not been fully investigated. We evaluated the clinical features and prognosis of seeding. MethodsWe included 4405 patients who had undergone surgery (lumpectomy or mastectomy) with a diagnosis of breast cancer by preoperative CNB or VAB at our hospital between January 2012 and February 2021. Data of patients with confirmed presence of seeding in resected specimens were collected from pathological records. We analyzed the risk factors of seeding using logistic regression analysis and compared the ipsilateral breast tumor recurrence (IBTR) rate between cases based on the presence or absence of seeding in the lumpectomy group. ResultsOf the 4405 patients, 133 (3.0%) had confirmed seeding. Univariate analysis revealed the association of clinicopathological features of seeding with lower nuclear grade (NG1 vs NG2-3; p = 0.043), lower Ki-67 (<30 vs. ≥30; p = 0.049), estrogen receptor (ER) positivity (positive vs negative; p<0.01), and human epidermal growth factor receptor 2 (HER2) negativity (negative vs positive; p = 0.016). Multivariate analysis showed ER positivity (odds ratio, 5.23; p<0.05) as an independent risk factor of seeding. The IBTR rate was not significantly different between the seeding and non-seeding groups. ConclusionsSeeding was more likely to occur in ER positive, HER2 negative carcinomas with less aggressive features, and may remain subclinical if adequate adjuvant treatments are administered.

Preferences Regarding Breast Surgery Omission Among Patients With Breast Cancer Who Receive Neoadjuvant Chemotherapy.

Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.

A prospective analysis of two studies that used the 5-mm interval slices and 5-mm margin-free method for ipsilateral breast tumor recurrence after breast-conserving surgery without radiotherapy

BackgroundBreast-conserving surgery with radiotherapy is one of standard treatments for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor-positive breast cancer with breast-conserving surgery and hormone therapy without radiotherapy. We conducted two sequential prospective studies to examine the feasibility of breast-conserving surgery without radiotherapy since 2002 and present the results.Patients and methodsPrimary female breast cancer patients who fulfilled the strict eligibility criteria were prospectively enrolled in two sequential studies named WORTH 1 and 2. The surgical materials were sliced in 5-mm intervals and all slices were examined microscopically. Postoperative radiotherapy was not allowed, but tamoxifen or anastrozole was administered for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival was the primary outcome.ResultsThe data of the two studies were combined (N = 321). The median follow-up period for IBTR was 94 months (4–192 months). Only three patients were treated with adjuvant chemotherapy. The 5- and 10-year IBTR-free rates were 97.0% and 90.5%, respectively. The age at operation and PR status affected IBTR rates independently. When we calculated IBTR-free rates of patients who were 65 years of age or older at the time of surgery and had PR-positive tumors, the 5- and 10-year IBTR rates were both 98.4%.Conclusions Our “5-mm-thick slice and 5-mm free-margin” method may be effective to select patients who can be treated by breast-conserving surgery and hormone therapy without radiotherapy.

Risk of ipsilateral breast tumor recurrence and contralateral breast cancer in patients with and without TP53 variant in a large series of breast cancer patients

BackgroundThe association between breast cancer patients with a TP53 pathogenic variant and risk of local recurrence and contralateral breast cancer remains largely unknown. MethodsThe study population of 11093 patients was derived from two cohorts at the Breast Center of Peking University Cancer Hospital in China from November 2003, to March 2018. TP53 germline variants were determined for all patients. ResultsIn the study, forty-one (0.37%) carried a TP53 germline pathogenic variant, and 11052 were non-carriers (99.63%). Nineteen TP53 carriers (46.3%) and 4173 non-carriers (37.8%) were treated with breast-conserving therapy (BCT), while the remaining were treated with mastectomy. After a median follow-up of 6.7 years, the rate of ipsilateral breast tumor recurrence (IBTR) in TP53 carriers was significantly higher than that in non-carriers when treated with BCT (21.1% vs 3.8%, P = 0.006). No difference in the rate of IBTR was found between TP53 carriers and non-carriers when treated with mastectomy (0.0% vs 2.6%, P = 1.0). Furthermore, the rate of IBTR in TP53 carriers treated with BCT was significantly higher than that in those treated with mastectomy (21.1% vs 0.0%, P = 0.038). The 10-year cumulative risk of contralateral breast cancer in TP53 carriers was significantly higher than that in non-carriers (17.9% vs 3.6%, hazard ratio (HR) = 7.0, 95% CI: 3.3–14.9, P < 0.001). ConclusionsPatients with TP53 variants have a high risk of IBTR when treated with BCT, and exhibit a very high risk of contralateral breast cancer. TP53 carriers may not be suitable for BCT and prophylactic contralateral mastectomy might be considered.

Surgical Options for Ipsilateral Breast Tumor Recurrence: Mastectomy Versus Repeat Breast-Conserving Surgery

Purpose: The standard care for patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) is a total mastectomy (TM); however, there is growing interest in repeating BCS for IBTR.Methods: We retrospectively analyzed patients with IBTR who underwent initial BCS for breast cancer at our institution between January 2000 and December 2018. The Kaplan-Meier method was used to compare survival rates between the standard BCS-TM treatment group and the repeat-BCS group.Results: We enrolled 209 IBTR patients with a median follow-up of 102.3 months. No significant differences were observed in overall survival (10 years: 87.3% vs. 78.8%; hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.44-2.81; p=0.821), distant metastasis free survival (10 years: 73.9% vs. 77.7%; HR, 0.80; 95% CI, 0.37-1.72; p=0.727) and disease-free survival (10 years: 57.1% vs. 65.2%; HR, 0.63; 95% CI, 0.35-1.12; p=0.115) between two groups. Repeat-BCS group showed significantly poorer locoregional recurrence free survival rate than did the TM group (HR, 2.44; 95% CI, 1.06-5.56; p=0.029) but the significance was not shown after excluding ipsilateral breast tumor recurrence events.Conclusion: No significant differences were observed in survival outcomes and recurrence rates between patients with IBTR who underwent mastectomy or repeat BCS regardless of molecular subtype, except secondary IBTR rates.

Effect of neoadjuvant versus adjuvant chemotherapy on ipsilateral breast tumor recurrence after breast-conserving surgery and whole-breast irradiation.

604 Background: Early Breast Cancer Trialists’ Collaborative Group conducted a large meta-analysis and reported that patients who underwent neoadjuvant chemotherapy (NAC) had higher ipsilateral breast tumor recurrence (IBTR) rate than those with adjuvant chemotherapy. However, since the study was conducted with patients treated two decades ago, the results could not reflect the advance in treatments and IBTR rate was much higher than in recent studies, Thus, we investigated the association between chemotherapy settings and IBTR rates in breast cancer patients. Methods: We retrospectively reviewed the data of 5,307 patients who underwent breast conserving surgery followed by whole breast irradiation between January 2004 and December 2018 in a single institution. Patients who underwent mastectomy or omitted chemotherapy were excluded. Results: The 1,473 patients who underwent NAC showed significantly higher IBTR rate than the 3,564 patients who underwent adjuvant chemotherapy (10-year risk: 4.5% vs. 4.0%; log-rank p=0.045, hazard ratio 1.42 [95%CI,1.01-1.99]). The difference was more evident for patients with hormone receptor (HR) positive and human epidermal growth factor receptor-2 (HER2) negative tumor (unadjusted p=0.001, hazard ratio 2.27 [95%CI,1.37-3.74; adjusted p=0.002, hazard ratio 2.80 [95%CI,1.45-5.42]], and the statistical significance was still remained after 1:1 propensity score matching (p=0.026). In contrast, patients with other subtypes did not show significant differences between two groups. Conclusions: Patients who underwent NAC for HR+/HER2- tumors carry increased risk of IBTR than those who underwent adjuvant chemotherapy. Our observation supports the need for considering tumor subtypes in initial treatment. In addition, more intensive surveillance would be needed for patients with HR+/HER2- tumors after NAC.

Clinical Course and Predictors of Subsequent Recurrence and Survival of Patients With Ipsilateral Breast Tumor Recurrence.

PurposeTo evaluate the clinical course and long-term outcomes of patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and identify independent prognostic factors for further recurrence.MethodsIn this retrospective study, we reviewed the records of 327 patients who experienced IBTR after undergoing BCS for breast cancer at Asan Medical Center during 1990–2013. Overall survival (OS) after IBTR and cumulative incidence rates of recurrences after IBTR were calculated. The association of clinicopathological factors with survival and the development of further recurrence after IBTR was determined in multivariate analysis.ResultsAt a median follow-up of 127.7 months, 97 patients experienced recurrence after IBTR. The 5-year and 10-year cumulative incidence rates of recurrence after IBTR were 32% and 41%, respectively. The 5-year and 10-year OS rates after IBTR were 86.6% and 70.3%, respectively. In multivariate analysis, hormone receptor negativity was associated with decreases in OS after IBTR (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.18–6.78). Patients with longer disease-free interval (DFI) had decreased risks of second recurrence (HR .99, 95% CI .99–1.00), and second locoregional recurrence (LRR) (HR .98, 95% CI .97–.99). Lymphovascular invasion (LVI) of IBTR was associated with increased recurrence rates (second recurrence-free survival, HR 3.58, 95% CI 2.16–5.94; second LRR free survival, HR 5.21, 95% CI 2.77–9.78; second distant metastasis-free survival, 2.11, 95% CI 1.04–4.30) and lower survival rates (OS after IBTR, HR 4.64, 95% CI 2.23–9.67).ConclusionsDespite subsequent recurrences during long-term follow-up, the survival rates after IBTR remained high. Patients with hormone receptor-negative tumors, shorter DFI, and tumors that present LVI of IBTR had higher risks for recurrence and poor survival rates after IBTR. The study findings may help in understanding the course and prognosis of IBTR patients and identifying high-risk IBTR to establish management strategies.

A propensity score-matched analysis of breast-conserving surgery plus whole-breast irradiation versus mastectomy in breast cancer.

Recent observations regarding long-term outcomes among patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS) plus whole-breast irradiation (WBI) or mastectomy are from a small number of registry-based studies. Therefore, these findings may overestimate differences in survival between the two groups, compared with randomized controlled trials conducted in the 1980s. The aim of this study is to compare long-term outcomes and clinicopathologic characteristics between patients treated with BCS + WBI or mastectomy for BC. We performed a propensity score-matched analysis in a cohort of 9710 patients aged < 70years who underwent BCS + WBI or mastectomy without external radiotherapy for a first primary BC (pT1-2, N0-3a) at the European Institute of Oncology between 2000 and 2008. Patients were matched by propensity score. Median follow-up was 8.4years (interquartile range 6.5-10.2). The cumulative incidence of axillary lymph node recurrence at 10years was lower in the BCS + WBI group [2.4% (95% CI, 1.7-3.3%)] than in the mastectomy group [4.4% (95% CI, 3.5-5.5%)] (P = .0005), and the cumulative incidence of contralateral BC was higher in the BCS + WBI group [3.9% (95% CI, 2.8-5.1%)] than in the mastectomy group [2.5% (95% CI, 1.7-3.4%)] (P = .01). Among the 366 patients with HER2 subtype BC, BCS + WBI was associated with a fivefold higher risk [hazard ratio 4.97 (95% CI, 2.28-10.8)] of ipsilateral breast tumor recurrence (IBTR), compared with mastectomy (P < .0001); however, among patients with other BC subtypes, the rates of IBTR were not statistically significantly different. Patients with HER2 subtype BC (T1-2, N0-3) who underwent BCS + WBI had a statistically significantly higher risk of IBTR than patients who underwent mastectomy. Survival was not statistically significantly different between the groups.

Abstract P3-19-12: Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial

Abstract Purpose: To investigate the association between ET noncompliance and ipsilateral breast tumor recurrence (IBTR) in the ExBRT trial (“A Safety and Efficacy Study of Intra-Operative Radiation Therapy [IORT] Using the Xoft® Axxent® Electronic Brachytherapy [eBx®] System at the Time of Breast Conservation Surgery for Early-Stage Breast Cancer”). Methods: The IRB-approved single arm prospective nonrandomized multi-institutional ExBRT trial was designed to determine the efficacy and outcome of a single 20 Gy fraction of IORT delivered at the time of lumpectomy for early-stage breast cancer. The trial included women age ≥ 40 years with invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) of all molecular subtypes documented by pre-operative biopsy which were ≤ 30 mm by clinical and radiographic evaluation. Tumors with pre-operative lymphovascular invasion and intra-operative positive lymph nodes and/or margins were excluded. ET was defined as treatment with tamoxifen, anastrozole, letrozole, and/or exemestane. Pts were classified as “Compliant with ET” if they completed a 60-month ET course or were compliant with ongoing ET. Pts were defined as “Discontinued ET” if they stopped ET prior to completing a 60-month ET course. Pts were classified as “Declined ET” if they did not initiate recommended ET. Data, collected at enrollment and at 1, 6, 12, 18 and 24 months, then yearly, included demographics, histopathology, estrogen receptor positivity (ER+), progesterone receptor positivity (PR+), adjuvant therapy, IBTR, and survival. The primary endpoint was IBTR. Preliminary results evaluating the impact of ET noncompliance on pts who successfully completed treatment with a single 20 Gy fraction of IORT per protocol are presented. Results: Between May 2012 - July 2018, 1105 pts (mean age 64 years) with pre-operative biopsy-proven IDC or DCIS successfully completed a single fraction of IORT treatment per protocol. Mean follow-up was 4.0 years (range 2-8 years). One-hundred fifteen (10%) pts, who were either ER negative or had an unknown ER status, are not included in this analysis. Pt cohorts and tumor characteristics are presented in Table 1. There were 39 (3.93%) IBTR in the ER+ subset at mean follow-up of 4 years. IBTR in the “Compliant with ET” group was 2.53%. Although the percentages were greater in the “Discontinued ET” (5.68%) and “Declined ET” (7.10%) cohorts, this did not reach statistical significance (Chi square test, p-value = 0.147). Conclusion: IORT allows pts to conveniently receive both their surgery and electronic brachytherapy radiation treatment in one setting. Early-stage ER+ breast cancer pts compliant with a subsequent course of ET in this study experienced a lower IBTR rate, improving the collective outcome of their multidisciplinary treatment. These preliminary ExBRT trial results demonstrate that IBTR rates are improved with ET compliance. Although this has not reached statistical significance in this trial, it may partially explain the slight differences in IBTR rates noted in comparison with similar electronic brachytherapy early-stage breast cancer studies. Table 1.IORT pt cohorts and tumor characteristicsCompliant with ETDiscontinued ETDeclined ETNNNER +631176183PR +597170162Mean age (years)65.766.366.7Postmenopausal580162161Mean tumor size (mm)11.110.712.7Tumor HistologyIDC524136120grade I2116055grade II2535955grade III54159Unknown grade621DCIS933756Low grade2099Intermediate grade421925High grade30922Unknown grade100Infiltrating lobular ca505Other932Chemotherapy given4286Ethnicity/RaceCaucasian498143151African American351013Hispanic46188Asian/Pacific Islander2812Native American211Other2238Recurrences16 (2.53%)10 (5.68%)13 (7.10%) Citation Format: Barbara Schwartzberg, AMNisar Syed, Robert Cohen, William Dooley, Maen Farha, Veronica Jones, Wesley Hodge. Impact of endocrine therapy (ET) noncompliance following intra-operative radiation therapy (IORT) in treatment of early-stage breast cancer patients (pts) enrolled in the ExBRT trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-12.

Abstract PD7-09: Safety of conservative surgery with accelerated partial breast re-irradiation for isolated ipsilateral breast cancer recurrence regardless of immunohistochemical subtype. A multicentric prospective study

Abstract Background. The standard of care for patients (pts) with an ipsilateral breast tumour recurrence (IBTR) after breast conserving therapy (BCT) is a salvage mastectomy. However there is no solid data providing a clear advantage of radical surgery for IBTR in terms of the outcome for patients with isolated local recurrence after BCT. Nevertheless, there is a growing interest in the feasibility of repeating BCT for these patients (pts). We analyzed the oncological outcomes of repeated breast-conserving therapy (rBCT) related to the immunohistochemical subtype. Materials and methods. Between 2014 and 2020, 35 pts were selected for a 2nd BCT, a new lumpectomy with accelerated partial breast re-irradiation (APBrI), and prospectively followed in three university hospitals in Barcelona. Inclusion criteria were pts older than 50y with a late (&amp;gt; 48m from primary treatment) isolated IBTR less than 2cm, without having primary major radiotherapy toxicity. Oncological outcomes were analyzed. Results. At IBTR, median age was 65y and median time to ITBR was 154m. Patients characteristics are shown in table 1. Tumor’s recurrence was DCIS in 5 pts (14.3%) and invasive carcinoma in 30 pts (85.7%), where Luminal A in 10 pts (33.3%), Luminal B-HER2 negative in 12 pts (40%), Luminal B-HER2 positive in 2 (6.7%), non-Luminal HER2 positive in 3 (10%) and triple negative in 3 (10%). With a median follow-up of 37 months, there were 4 relapses (11.4%), one was a 2nd IBTR (2.85%) after in-situ IBTR, and 3 were metastatic recurrences (8.6%), two after invasive and one after in-situ IBTR. Both metastatic progressions after invasive IBTR, were hormone receptor positive and HER2 negative (Luminal B). There were 2 deaths not related with breast cancer. The 2nd IBTR rate was 2.85%. Five-year regional-free survival, metastasis-free survival, and overall survival was 82.4% (95% IC 52.6 - 94.4 %), %, 84.6% (95% IC 51 - 96 %) and 93.3% (95% IC 61.2 - 99%), respectively. Conclusion. Conservative treatment with breast conserving surgery and APBrI for isolated IBTR after BCT seems like a feasible technique as an alternative to mastectomy in selected patients. Second local recurrences and overall survival are similar to the rates described for salvage mastectomy for isolated ipsilateral breast tumour recurrence. In this cohort of patients, the immunohistochemical subtype tumors with poor prognosis (HER2 positive and triple negative) did not show increase in the local recurrence rate. Table 1.Patients Characteristicsn%Histology TypeIDC2777.1ILC0DCIS514.3Others38.6Differentiation gradeWell differentiated1028.6Moderately differentiated1851.4Poorly differentiated720Estrogen-receptor statusPositive2880Negative720Progesteron-receptor statusPositive1645.7Negative1748.6Unknown25.7HER2 statusOver-expressed617.1Non-over-expressed2674.3Unknown38.6Ki67&amp;lt; 20 %1748.6&amp;gt; 20 %1337.2Unknown514.3IHC subtypeLuminal A1033.3Luminal B1240Luminal B-HER2 positive26.7Non-luminal HER2 positive310Triple negative310IBTR locatedSame quadrant1748.6Different quadrant1645.7Unknwon25.7APBrI3D-CRT927.3IORT26.1IMRT2266.7 Citation Format: Martin Espinosa-Bravo, Victoria Reyes Lopez, Clara Morales Comas, Joaquín Rivero Déniz, Javier de La Torre Fernández de Vega, Irene Vives Roselló, Christian Sisó Raber, Manuel Altabas Gonzalez, Alexandra Giraldo Marin, Inma Alonso, Nuria Argudo, Pau Nicolau, Manel Algara, Xavier Sanz, Xavier Caparrós, Gabriela Oses, Jordi Saez, María Vernet-Tomas, Meritxell Mollà. Safety of conservative surgery with accelerated partial breast re-irradiation for isolated ipsilateral breast cancer recurrence regardless of immunohistochemical subtype. A multicentric prospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-09.

Abstract P3-19-19: Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes

Abstract Background: With TARGIT-R(Retrospective) showing a higher-than-expected ipsilateral breast tumor recurrence (IBTR) the community setting for intraoperative radiation therapy (IORT), we evaluated IORT outcomes in an integrated health care system.Methods: A retrospective review of early breast cancer patients who received IORT between February 2014-February 2020 was performed. IORT was offered at a single medical center within a large integrated healthcare system. Criteria for IORT included patients ≥50 years with T1, low to intermediate grade, endocrine-responsive HER2- invasive ductal carcinoma. All breast cancer patients were reviewed at weekly multidisciplinary breast conferences, and IORT was offered when patients met the eligibility criteria. Primary outcomes include IBTR, mortality, and complications. Results: Of 5,731 potentially eligible patients, 245 patients (4.3%) underwent IORT. Mean age was 65.4 ± 0.4 years with median follow-up 3.5 years ± 2.2 months. Based on American Society of Radiation Oncology guideline, 51% were suitable, 38.4% cautionary, and 10.6% unsuitable candidates based on the final pathology. The patients were reassigned to the cautionary group because of the margin width and/or extensive DCIS. Unintended boost (primary IORT followed by whole-breast radiation) was given in 6.5% of IORT patients. At median follow-up of 3.5 years, IBRT was 3.7% for all patients. There was one breast-cancer-related mortality (0.4%), and 7 mortality (2.9%) from other causes. Although not statistically significant, there was a trend towards higher recurrence in those not adherent with endocrine treatment than those who were (7.4% vs 1.9%, p=0.07). The overall complication rate was 14.7% with seroma as the most common.Conclusions: At 3.5-year follow-up, our IORT IBTR rate of 3.7%. Our protocol subsequently was modified to require all IORT patients to receive surgical shave margins, WBI for all cautionary patients on the final pathology, and requirement of endocrine treatment. Citation Format: Annie Tang, Jason Kelly, Elizabeth Cureton, Jonathan Svahn, Eva Thomas, Liisa Lyon, Veronica Shim. Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-19.

Comparison between the use of hypofractionated and conventionally fractionated radiotherapy in early breast cancer: A single-center real-world study in Taiwan

This study aimed to analyze the long-term outcomes of hypofractionated whole-breast irradiation (WBI) (HF-WBI) compared with those of conventionally fractionated WBI (CF-WBI) for early breast cancer treated with breast-conservation surgery (BCS) and adjuvant WBI in Taiwan. This study included patients treated at our institution between 2012 and 2016. All patients with early breast cancer received BCS (pT1-2, pN0, M0) and adjuvant WBI through one of two treatment schemes. Propensity score matching analysis was conducted to create comparable cohorts. The major result is ipsilateral breast tumor recurrence (IBTR) rates and overall survival rates. A total of 869 patients with early-stage breast cancer received adjuvant HF-WBI or CF-WBI were included. After matching, 718 patients were separated into two groups of the same number. With a median follow-up of 66 months, seven cases of IBTR were noted (three for CF, four for HF). There were no significant differences between the HF-WBI and CF-WBI groups in 5-year IBTR rates (0.9% vs 0.6%, P=0.3887, 95% CI [0.25-7.79]) and 5-year overall survival rates (98.1% vs 98.9%, P=0.4702, 95% CI [0.32-3.49]). In our institution, the use of HF-WBI increased significantly from 5% before 2012 (Q3) to 92% in 2016 (Q4). There was no significant difference in grade 1-2 toxicity between the two treatment groups. Fewer cases of grade 3 skin toxicity noted in the HF-WBI group (zero vs four events). HF-WBI had similar IBTR, OS and toxicity to CF-WBI.